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INTRODUCCIÓN: Voriconazol es el antifúngico de elección para el tratamiento de la aspergilosis invasora (AI). Concentraciones plasmáticas (CPs) > 1 μg/mL se han asociado a mejores resultados terapéuticos, las que no siempre se alcanzan durante el tratamiento en niños inmunocomprometidos. Dada la necesidad de iniciar una terapia precoz y efectiva de la infección, es relevante establecer el régimen de administración de voriconazol que se asocie con CPs óptimas en esta población. OBJETIVO: Comparar las CPs y seguridad de voriconazol intravenoso (IV), dosificado BID y TID en niños inmunocomprometidos con indicación de tratamiento antifúngico. MÉTODO: Estudio observacional retrospectivo de enero de 2015 a julio de 2018 en un hospital pediátrico de alta complejidad de Santiago de Chile, en pacientes de 0 a 17 años que recibieron tratamiento con voriconazol IV. Se excluyeron aquellos con terapia de reemplazo renal, falla hepática y/o falla renal. Se compararon las CPs valles entre un grupo con régimen de dosificación BID y otro grupo con administración TID. Se evaluaron las reacciones adversas en ambos grupos. RESULTADOS: Se obtuvieron 137 CPs valles en 76 niños, con una mediana de edad de 9 años (0-17 años) en el grupo BID y 9 años (0-16 años) en el grupo TID, con una mediana de peso de 27 kg (6-83 kg) y 28 kg (9,3-60 kg), respectivamente. Resultados: Pacientes 1 gg/mL en comparación con la administración BID (p = 0,001). Se reportaron ocho reacciones adversas, principalmente fotofobia, sin encontrarse diferencias significativas entre grupo BID y TID. CONCLUSIÓN: Dosificaciones TID están asociadas a una mayor probabilidad de obtener una adecuada exposición a voriconazol en pacientes < 12 años en comparación a dosificaciones BID, con baja frecuencia de reacciones adversas.
BACKGROUND: Voriconazole is the antifungal of choice for the treatment of invasive aspergillosis (IA). Plasma concentrations (PCs) > 1 μg / mL llave been associated with better therapeutic results which have not always been achieved during treatment in immunocompromised children. In the necessity to initiate early and effective therapy for the infection, it is relevant to establish the voriconazole administration regimen that is associated with optimal PCs in this population. AIM: To compare the PC and safety of intravenous (IV) voriconazole, dosed BID and TID in immunocompromised children with indication of antifungal treatment. METHOD: Retrospective observational study since January 2015 until July 2018 in a highly complex pediatric hospital in Santiago of Chile, in patients aged 0 to 17 years who received treatment with IV voriconazole. Those with renal replacement therapy, liver failure and / or renal failure were excluded. Trough PCs were compared between a group with BID dosing regimen versus another group with TID administration. Adverse reactions were evaluated in both groups. RESULTS: 137 trough PCs were obtained in 76 children, with a median age of 9 years (0-17 years) in the BID group and 9 years (0-16) in the TID group with a median weight of 27 kg (6-83 kg) and 28 kg (9.3-60 kg), respectively. Patients 1 gg/mL compared to BID administration (p = 0.001). Eight adverse reactions were reported, mainly photophobia, with no significant difference found between the BID and TID groups. CONCLUSION: TID dosages are associated with a greater probability of obtaining adequate exposure to voriconazole in patients < 12 years old compared to BID dosages, with a low frequency of adverse reactions.
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Humans , Male , Female , Infant, Newborn , Infant , Child, Preschool , Child , Adolescent , Aspergillosis/drug therapy , Invasive Fungal Infections , Pharmaceutical Preparations , Retrospective Studies , Voriconazole , Antifungal AgentsABSTRACT
OBJECTIVEP: To explore the relationship between multidrug resistance gene ABCB1 C3435T gene polymorphism and serum concentration, clinical efficacy and adverse reactions of levetiracetam (LEV) in children with epilepsy in Xinjiang. METHODS: The serum concentration of 116 children with epilepsy of in Xinjiang were collected and determined by oral LEV. The ABCB1 C3435T genotype was detected by polymerase chain reaction-fluorescence staining in situ hybridization. The correlation between ABCB1 C3435T gene polymorphism and serum concentration, clinical efficacy and adverse reactions was analyzed. RESULTS: The C and T allele frequencies of ABCB1 C3435T in children were significantly different (χ2=12.520, P0.05). The clinical effective rate of CT type was higher than that of CC type and TT type, and the incidence of adverse reactions of TT type was higher than that of CC type and CT type. There were significant differences in clinical efficacy and adverse reactions among CC type, CT type and TT type (χ2=12.870,P<0.01; χ2=19.292, P<0.01). CONCLUSION: ABCB1 C3435T gene polymorphism may has a effect on the serum concentration, clinical efficacy and adverse reactions of LEV in children with epilepsy in Xinjiang.
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Objective@#To evaluate trough serum vancomycin concentrations and identify their influencing factors in critically ill neurosurgical patients.@*Methods@#A retrospective study was conducted. Adult patients who received vancomycin with at least one appropriate monitoring of trough serum vancomycin concentration and admitted to neurosurgical intensive care unit (ICU) of the First Affiliated Hospital of Sun Yat-sen University from November 2017 to July 2019 were enrolled. General information including gender, age, comorbidities, etc., trough serum vancomycin concentrations, vancomycin dosage, duration of vancomycin therapy, urine output, serum creatinine (SCr), concurrent medications (including mannitol, diuretic, vasopressors, non-steroidal anti-inflammatory drugs, polymyxin, aminoglycosides and contrast medium, etc.) were collected for analysis. Trough serum vancomycin concentrations were evaluated and their influencing factors were analyzed by multiple linear regression method.@*Results@#In total, 81 trough serum vancomycin concentration data sets obtained from 28 patients were evaluated. ① The initial daily dose of vancomycin was 2.00 (2.00, 2.00) g/d. After 4-6 doses, the trough serum vancomycin concentration obtained from initial blood draw was 10.99 (6.98, 16.25) mg/L, of which only 17.9% (5/28) achieving targeted concentrations (15-20 mg/L), 71.4% (20/28) subtherapeutic level and 10.7% (3/28) supratherapeutic level. ② The duration of vancomycin therapy was 8.0 (6.0, 15.0) days. With average daily dose of 2.00 (1.75, 3.00) g/d, targeted trough vancomycin concentrations were achieved in only 30.9% (25/81) of all cases, subtherapeutic concentrations in 49.4% (40/81) and supratherapeutic concentrations in 19.7% (16/81). ③ There were significant differences in age, comorbidities, vancomycin dosage, diuretics use and mannitol dosage, etc. among different vancomycin concentration groups. Multiple linear regression analysis suggested that the trough serum vancomycin concentration increased by 0.14 mg/L [95% confidence interval (95%CI) was 0.06-0.22] for every 1 year increase in age, increased by 7.22 mg/L (95%CI was 2.08-12.36) in patients with multiple comorbidities (concomitant hypertension, diabetes and coronary heart disease) compared with those without comorbidities, increased by 2.78 mg/L (95%CI was 0.20-5.35) in patients treated with diuretics compared with those without diuretics. The effect of other variables was not statistically significant. It suggested that age, multiple comorbidities (concomitant hypertension, diabetes and coronary heart disease), and diuretic usage affected trough serum vancomycin concentrations.@*Conclusions@#Targeted trough serum vancomycin level is not often achieved in neurosurgical ICU patients following standard dosing. Younger patients are associated with lower trough serum vancomycin concentrations, while diuretic usage, combined with multiple comorbidities are associated with higher trough serum vancomycin concentrations.
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To evaluate trough serum vancomycin concentrations and identify their influencing factors in critically ill neurosurgical patients. Methods A retrospective study was conducted. Adult patients who received vancomycin with at least one appropriate monitoring of trough serum vancomycin concentration and admitted to neurosurgical intensive care unit (ICU) of the First Affiliated Hospital of Sun Yat-sen University from November 2017 to July 2019 were enrolled. General information including gender, age, comorbidities, etc., trough serum vancomycin concentrations, vancomycin dosage, duration of vancomycin therapy, urine output, serum creatinine (SCr), concurrent medications (including mannitol,diuretic, vasopressors, non-steroidal anti-inflammatory drugs, polymyxin, aminoglycosides and contrast medium, etc.) were collected for analysis. Trough serum vancomycin concentrations were evaluated and their influencing factors were analyzed by multiple linear regression method. Results In total, 81 trough serum vancomycin concentration data sets obtained from 28 patients were evaluated. ① The initial daily dose of vancomycin was 2.00 (2.00, 2.00) g/d. After 4-6 doses, the trough serum vancomycin concentration obtained from initial blood draw was 10.99 (6.98, 16.25) mg/L, of which only 17.9% (5/28) achieving targeted concentrations (15-20 mg/L), 71.4% (20/28) subtherapeutic level and 10.7% (3/28) supratherapeutic level. ② The duration of vancomycin therapy was 8.0 (6.0, 15.0) days. With average daily dose of 2.00 (1.75, 3.00) g/d, targeted trough vancomycin concentrations were achieved in only 30.9% (25/81) of all cases, subtherapeutic concentrations in 49.4% (40/81) and supratherapeutic concentrations in 19.7% (16/81). ③ There were significant differences in age, comorbidities, vancomycin dosage, diuretics use and mannitol dosage, etc. among different vancomycin concentration groups. Multiple linear regression analysis suggested that the trough serum vancomycin concentration increased by 0.14 mg/L [95% confidence interval (95%CI) was 0.06-0.22] for every 1 year increase in age, increased by 7.22 mg/L (95%CI was 2.08-12.36) in patients with multiple comorbidities (concomitant hypertension, diabetes and coronary heart disease) compared with those without comorbidities, increased by 2.78 mg/L (95%CI was 0.20-5.35) in patients treated with diuretics compared with those without diuretics. The effect of other variables was not statistically significant. It suggested that age, multiple comorbidities (concomitant hypertension, diabetes and coronary heart disease), and diuretic usage affected trough serum vancomycin concentrations. Conclusions Targeted trough serum vancomycin level is not often achieved in neurosurgical ICU patients following standard dosing. Younger patients are associated with lower trough serum vancomycin concentrations, while diuretic usage, combined with multiple comorbidities are associated with higher trough serum vancomycin concentrations.
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In view of the fact that cancer is considered a chronic disease that can interfere with hormonal homeostasis by means of cytokines, we hypothesized that, even at early stages, mammary carcinoma is able to alter the balance of the hypothalamic-pituitary-thyroid and hypothalamic-pituitary-adrenal axes. To test this hypothesis, the serum concentrations of basal cortisol, thyroxine (T4), free thyroxine (fT4), and thyroid-stimulating hormone (TSH) were evaluated in 20 unspayed bitches that had a histopathological diagnosis of grade 1 mammary carcinoma at clinical stage I according to the World Health Organization (WHO) classification (T1N0M0). The control animals comprised 10 unspayed bitches in perfect health conditions that were matched with those with mammary carcinoma by age. No significant differences regarding the concentrations of basal cortisol, TSH, t4, and fT4 were found between the bitches carrying early stage mammary carcinoma when compared to the control group. This suggests that, even if malignant, early-stage mammary carcinomas do not exhibit the ability to alter the concentrations of hormones produced by the hypothalamic-pituitary-adrenal or hypothalamic-pituitary-thyroid axes.(AU)
Em vista do fato de neoplasias serem consideradas doenças crônicas que por meio de citocinas podem interferir na homeostase hormonal, hipotetizou-se que o carcinoma mamário, mesmo nos seus estádios iniciais, fosse capaz de alterar o equilíbrio dos eixos hipotalâmico-hipofisário-tireóideo e hipotalâmico-hipofisário-adrenal. Para tal, foram avaliadas as concentrações séricas de cortisol basal, tiroxina (T4), tiroxina livre (fT4) e tireotrofina (TSH) de 20 fêmeas caninas, inteiras, com diagnóstico histopatológico de carcinoma mamário grau 1 e estadiamento clínico I segundo a classificação da Organização Mundial da Saúde - OMS (T1N0M0). Os animais controle constituíram-se por 10 fêmeas caninas inteiras, em perfeitas condições de higidez, as quais foram pareadas, por idade, com aquelas portadoras de carcinoma mamário. Não foram encontradas diferenças significativas nas concentrações de cortisol basal, TSH, T4 e fT4 das cadelas portadoras de carcinoma mamário em estádio inicial quando comparadas às controles sugerindo que, mesmo considerados malignos, ainda não apresentam a capacidade de alterar as concentrações dos hormônios produzidos pelos eixos hipotalâmico-hipofisário-adrenal e tireóideo.(AU)
Subject(s)
Animals , Dogs , Pituitary-Adrenal System , Mammary Neoplasms, Animal/diagnosis , Dogs/blood , Hypothalamo-Hypophyseal SystemABSTRACT
O objetivo desse estudo foi avaliar as concentrações séricas de estradiol, progesterona e prolactina, bem como a expressão gênica dos receptores de estrógeno α e β e de progesterona em cadelas com neoplasias mamárias. Foram utilizadas 60 cadelas adultas, sem raça definida que foram distribuídas em dois grupos. O Grupo I constituído por 30 cadelas portadoras de neoplasias mamárias e o Grupo II constituído por 30 cadelas saudáveis, não portadoras de neoplasia. Para os tutores, foram aplicados questionários sobre fatores epidemiológicos da doença. Após avaliação dos exames pré-operatórios, as cadelas com neoplasia mamária foram submetidas à mastectomia, coletaram-se fragmentos das neoplasias e linfonodos regionais, os quais foram processados para análise histopatológica. Para as dosagens hormonais de estradiol, progesterona e prolactina foram colhidas amostras de sangue em tubos sem anticoagulante e os soros foram submetidos à técnica de eletroquimioluminescência. A expressão gênica dos receptores hormonais foi realizada por meio da técnica de Real-time PCR e para isso foram coletados fragmentos das neoplasias mamárias e extraído o RNA para obtenção do cDNA. A expressão do mRNA para os REα, REβ e RP foi avaliada a partir da amplificação desses genes utilizando primers específicos. Verificaram-se maiores níveis séricos de estradiol (média de 38,98±13,68pg/mL) em cadelas portadoras de neoplasias mamárias malignas quando comparadas as cadelas do grupo controle (p<0,05). Já os níveis séricos de prolactina foram maiores (média de 0,231±0,201ng/mL) nas cadelas que não possuíam neoplasias mamárias quando comparadas ao Grupo I (p<0,05). Para os níveis de progesterona não foram observadas diferença entre os diferentes grupos (p>0,05). Tanto os tumores malignos como os benignos expressaram REα, REβ e RP, não havendo diferença (p>0,05) na expressão entre tumores malignos ou benignos ou relacionada aos outros fatores prognósticos investigados (estadiamento clínico, presença de ulceração, vascularização e tempo de evolução do processo). Os níveis séricos de estradiol aumentaram significativamente com o estadiamento clínico da doença (p<0,05). Verificou-se moderada correlação negativa entre os níveis séricos de estradiol e prolactina. Dessa forma, conclui-se que as dosagens séricas de estradiol e PRL foram influenciadas pela malignidade do tumor e pelo estadiamento clínico das neoplasias. Os receptores hormonais foram expressos pelas neoplasias, independentemente do tipo tumoral e não estão associados aos outros fatores prognóstico clássicos, como presença de ulceração, vascularização ou estadiamento clínico.(AU)
The aim of this study was to evaluate the serum concentrations of estradiol, progesterone, prolactin, the gene expression of estrogen α and β and progesterone receptors in bitches with mammary neoplasms. Sixty adult crossbred bitches distributed in two groups were used. Group I consisted of 30 bitches with mammary neoplasms and Group II consisted of 30 healthy bitches without neoplasia. For the tutors, interviews were made about the disease epidemiology. After preoperative examinations, bitches with mammary neoplasia were submitted to mastectomy; fragments of the neoplasms and regional lymph nodes were collected and processed for histopathological analysis. Blood samples were collected in tubes without anticoagulant and the serum was analyzed by electrochemiluminescence to measure estradiol, progesterone and prolactin. The gene expression of the hormonal receptors was performed by means of the Real-time PCR technique, thus fragments of mammary neoplasms were collected and the RNA was extracted to obtain cDNA. Expression of the mRNA for ERα, ERβ and PR was assessed from the amplification of these genes using specific primers. Higher serum levels of estradiol (mean 38.98±13.68pg/mL) were observed in bitches with malignant neoplasms when compared to the control bitches (p<0.05). Serum prolactin levels were higher (mean of 0.231±0.201ng/mL) in bitches that did not have mammary neoplasms when compared to Group I (p<0.05). No difference was observed for related to the progesterone levels between the groups (p>0.05). Both malignant and benign tumors expressed ERα, ERβ and RP with no statistical difference (p>0.05) and there were no difference related to the other prognostic factors investigated (clinical staging, presence of ulceration, vascularization and aging of neoplasms). Serum estradiol levels increased significantly with the clinical staging of the disease (p<0.05). There was a moderate negative correlation between serum levels of estradiol and prolactin. It was concluded that serum levels of estradiol and PRL were influenced by tumor malignancy and clinical staging of neoplasms. Hormonal receptors were expressed by neoplasms, regardless of tumor type and are not associated with other classical prognostic factors, such as ulceration, vascularization or clinical staging.(AU)
Subject(s)
Animals , Female , Dogs , Progesterone/chemical synthesis , Breast Neoplasms/enzymology , Dogs/abnormalities , Estrogens/chemical synthesisABSTRACT
Objective To analyze the distribution characteristics of vancomycin blood concentration in children with severe pneumonia complicated with congenital heart disease( CHD) and children with simple severe pneumonia after using the same dose vancomycin,and observe the clinical efficacy at the same time. Methods Plasma concentrations in pediatric patients with severe pneumonia complicated with CHD ( CHD group) who treated by vancomycin from November 2012 to September 2013 in Shengjing Hospital of China Medical University were collected. Plasma concentrations of children with simple severe pneumonia( control group) treated by vancomycin were also collected at the same period. The blood concentration values and therapeutic effects of the two groups were recorded into the database for statistical analysis. Peak,trough con-centrations and efficacy were analyzed by receiver operating characteristic(ROC) curve. Results Twenty-five children with CHD were collected,the average peak concentration was (28. 39 ± 6. 68) mg/L,the aver-age trough concentration was (13. 34 ± 6. 62)mg/L. Control group were also 25 cases,the average peak con-centration was (16. 23 ± 2. 50) mg/L and the average trough concentration was (2. 77 ± 1. 01) mg/L. Both peak and trough concentrations of CHD children were significantly higher than those of the control group (tpeak =8. 52,Ppeak <0. 05;ttrough =7. 89,Ptrough <0. 05). In the ROC of peak,trough concentrations and effica-cy,area under the curve were 0. 74(95％CI 0. 547-0. 935,P=0. 01) and 0. 77(95％CI 0. 605-0. 935,P=0. 004) respectively,and the difference was statistically significant. Conclusion Plasma concentrations of vancomycin in children with CHD are generally higher,it is necessery to monitor plasma concentration even under regular doses,to make the application of vancomycin more safe and effective in children with CHD. There is a correlation between plasma concentration of vancomycin and clinical efficacy in children,the high-er the blood concentration,the more likely the clinical efficacy is to be effective.
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OBJECTIVE: Citalopram (CITA) is a widely used and well-tolerated selective serotonin reuptake inhibitor. The aim of the study was to evaluate the possible influences of serum concentrations of CITA and its major metabolite n-desmethylcitalopram (NDCITA) on the efficacy and tolerability of CITA in patients with major depressive disorder. METHODS: The study included 46 outpatients with major depressive disorder who received CITA. The efficacy and tolerability were assessed for 6 weeks. Serum CITA and NDCITA levels were measured at the 4th week. RESULTS: The HDRS17 total scores of the patients with high NDCITA and CITA & NDCITA concentrations showed a more significant reduction compared to the patients with expected and low serum NDCITA and CITA & NDCITA concentrations. However, we did not observe a correlation between the serum concentrations and the side effects of CITA, NDCITA, and CITA & NDCITA. CONCLUSION: Our results suggested the potential contribution of NDCITA to the antidepressant effect of CITA. Further studies involving larger clinical samples are required to confirm the impact of serum NDCITA concentrations on the efficacy of CITA.
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Humans , Citalopram , Depression , Depressive Disorder, Major , Outpatients , SerotoninABSTRACT
@#AIM: To study the serum lipids changes in patients with Leber congenital amaurosis(LCA).<p>METHODS: Based on the retrospective study and the simple size in the statistics, 50 cases of LCA patients and 52 cases of normal people were included. The serum levels of low density lipoprotein cholesterol(LDL-C), high density lipoprotein cholesterol(HDL-C), triglycerides(TG), and total cholesterol(TC)were measured by professionals in hospital according to the single blind study. Data were analyzed statistically between the LCA group and normal group. <p>RESULTS: Among the 50 patients with LCA, abnormal serum lipid content accounted for 46%, of which 26% were low in HDL-C levels, hypertriglyceridemia accounted for 48%, hypercholesteremia accounted for 17%, respectively, 9% of patients had mixed hyperlipidaemia. The serum level of HDL-C was 1.221±0.317mmol/L in the LCA group, which was significantly lower than the normal group(<i>P</i><0.05). The serum levels of TG and TC were 1.377±1.171mmol/L and 4.506±0.694mmol/L<sup> </sup>in the LCA group, which were significantly higher than the normal group(all <i>P</i><0.01). There was no significant difference in the serum level of LDL-C between LCA and normal group(<i>P</i>>0.05). <p>CONCLUSION: In patients with LCA, abnormal concentration changes of HDL-C,TG and TC may be associated with the occurrence of LCA.
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Objective: To analyze the serum concentration results of sodium valproate (VPA) and carbamazepine (CBZ) and explore the relationship between the serum concentration and age, clinical efficacy and adverse reactions to provide reference for the rational clinical use.Methods: Retrospective analysis was used to collect the clinical data of the patients from March 2015 to March 2016, including gender, age, clinical diagnosis, medication, usage and dosage, the last medication time, sampling time, blood concentration and the other related data, and the data were compared and analyzed.Results: Totally 2608 samples were collected, including 2 205 ones for VPA and 403 ones for CBZ.Totally 1 123 cases (50.93%) of VPA and 292 cases (72.46%) of CBZ were within the range of therapeutic windows.In the 2 205 cases of VPA, 1 814 cases (82.27%) were with single drug treatment, and the serum concentration lower than the lower limit of therapeutic window accounted for 790 cases (43.55%) with the effective rate of 43.55% for epilepsy.The serum concentration within the range of therapeutic window accounted for 921 cases (50.77%) with the effective rate of 88.27% for epilepsy, and that higher than the higher limit of therapeutic window accounted for 103 cases (5.68%) with the effective rate of 81.55%.As for CBZ, the number was 58 cases (22.39%) with the effective rate of 48.28%, 195 cases (72.29%) with the effective rate of 79.49% and 6 cases (2.32%) with the effective rate of 83.34%, respectively.Totally 391 cases (87.21%) of VPA combined with the other antiepileptic drugs, such as levetiracetam and lamotrigine.The effect of age on the serum concentration of VPA and CBZ was significant (P<0.05).Conclusion: There are great individual differences in serum concentration of VPA and CBZ among patients.The therapeutic effect and adverse reactions of VPA and CBZ are closely related to the serum concentration.Monitoring the serum concentrations may provide evidence for the rational administration and plays an important role in the treatment of epilepsy.
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Objective:To determine the concentration of meropenem in human serum and investigate its pharmacokinetics in Chi-nese elderly patients. Methods:Meropenem with single dose of 0. 5-1. 0 g was given to 25 elder patients by infusion administration. The concentration of meropenem was detected by an HPLC method. The pharmacokinetic parameters were calculated according to the pharmacokinetic model for adults and T>MIC was calculated by simple mathematical simulation. Results: The major pharmacokinetics parameters were as follows:Cmax of (46. 2 ± 24. 4) μg·ml-1;t1/2 of (3. 3 ± 1. 8) h,CL of (8. 7 ± 5. 0) L·h-1 ,V of (9. 8 ± 1. 3) L and AUC of (148. 2 ± 75. 4)μg·h·ml-1 . Compared with that of the healthy subjects reported in the literatures, t1/2 significantly pro-longed, V significantly decreased and AUC significantly increased (P<0. 01). Conclusion: The pharmacokinetics of meropenem in elder patients is significantly different from the healthy subjects. The clinical application should pay attention to monitoring the blood concentration of meropenem.
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OBJECTIVE:To compare the difference in the concentration determination of valproie acid (VPA) in human serum by LC-MS/MS and EMIT.METHODS:Both LC-MS/MS and EMIT methods were applied to determine the serum concentration of VPA in 144 inpatients or outpatients.The paired t-test,Pearson correlation analysis,Bland-Altman deviation chart and other methods were used to evaluate the difference in the results of concentration determination.RESULTS:The results of LC-MS/MS method was pos itively correlated with that of EMIT method (r=0.924,P＜0.05);the regression equation of them was cEMIT=0.920 7cLC.MS/MS-1.114 4 (r=0.924).Average serum concentrations of VPA determined by LC-MS/MS and EMIT were (49.9 ± 21.2) and (54.9 ± 21.3) μg/mL,with statistical significance (P＜0.05).The serum concentration of VPA determined by EMIT was higher than that by LC-MS/MS 8.3 μg/mL,95％ confidence interval was (-13.6,18.7).CONCLUSIONS:The serum concentration of VPA determined by LC-MS/MS and EMIT have high correlation.But the determination results still have certain difference,it is suggested to use same method for long term monitering.
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@#AIM:To study the concentration changes of the serum magnesium, calcium, potassium, sodium and chloride ions of the patients of Leber congenital amaurosis(LCA).<p>METHODS:Based on the retrospective study and the simple size in the statistics, 50 cases of LCA patients and 99 cases of normal people were tested the serum ions by professionals in hospital according to the single blind study. Data were analyzed statistically between LCA and normal groups. <p>RESULTS: In the clinical serum ions test of LCA group, the concentration of calcium and potassium were 2.338±0.090mmol/L and 4.164±0.356mmol/L respectively, which were significantly higher than those of the normal group(all <i>P</i><0.05), but the concentration of magnesium was 0.835±0.059mmol/L, which was significantly lower than the normal group(<i>P</i><0.05). There were no significantly differences in remainder two serum ions concentration of LCA groups,comparing with the normal group(all <i>P</i>>0.05). <p>CONCLUSION: In the patients with LCA, abnormal concentration changes of magnesium, calcium and potassium will be needed to concern of the ophthalmologist, which is probably related with the occurrence of LCA.
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Background: Voriconazole (VCZ) serum drug levels (SDL) vary widely and are associated with increased mortality when they are below the therapeutic range for invasive aspergillosis (IA). Aim: To describe VCZ SDL in oncology pediatric patients in order to reach adequate concentrations for prophylaxis (≥ 0.5 mg/L) and treatment (≥ 1.0 y 2.0 mg/L) for IA and their relationship with toxicity. Patients and Methods: Retrospective analysis of VCZ SDL and toxicities recorded in oncology pediatric patients between February 2013 and November 2014. The daily dosage and SDLs were analyzed according to administration route: intravenous (IV) and oral (PO), type of therapy (prophylaxis and treatment) and patient age (< 12 y ≥ 12 years old). Results: 112 through levels from 26 patients were analyzed and the average age was 9.3 years-old. The SDL obtained from the IV route were 43.7%. There were more SDL ≥ 0.5 mg/L and ≥ 1.0 mg/L with the IV route than the PO route (p < 0.05). Patients younger than 12-years-old received a higher dosage than those ≥ 12 years old (median 18.6 and 9.2 mg/kg/d, respectively, p < 0.05). To reach SDL ≥ 0,5 mg/L with the PO route, a dosage of 200 mg every 12 hours showed the best results for all patients (80-100% SDL ≥ 0.5 mg/L). With an IV dosage between 14 and 20 mg/kg/day in patients > 12-years-old, 80% of the SDL were ≥ 1 mg/L and ≥ 2 mg/L. In patients younger than 12-year-old, dosages between 8-30 mg/ kg/day showed similar results (50-63% of SDL ≥ 1 mg/L and 36-40% of SDL ≥ 2 mg/L). Eight patients (30.8%) presented an adverse drug reaction and no relationship with the SDL was found. Conclusión: A VCZ standard dosage of 200 mg every 12 hours PO showed the best results for IA prophylaxis in all patients. Patients younger than 12-years-old would require higher dosages than the doses used in this study to attain adequate SDL for IA treatment. No relation with SDL and adverse reactions was found.
Introducción: Las concentraciones plasmáticas (CPs) de voriconazol (VCZ) son erráticas y en el caso de encontrarse bajo rango terapéutico para el tratamiento de aspergilosis invasora (AI) se asocian a un aumento de mortalidad. Objetivo: Analizar las CPs de VCZ obtenidas en pacientes pediátricos para alcanzar valores que se estiman efectivos para profilaxis (≥ 0,5 mg/L) y tratamiento (≥ 1,0 y 2,0 mg/L) de AI y su relación con toxicidades. Pacientes y Métodos: Análisis retrospectivo de CPs de VCZ y toxicidades asociadas obtenidas en pacientes oncológicos pediátricos desde febrero de 2013 hasta noviembre 2014. Se analizó la dosis diaria y CPs de acuerdo a la vía de administración: intravenosa (iv) u oral (vo), tipo de terapia (profilaxis y tratamiento) y edad (< 12 y ≥ 12 años). Resultados: Se analizaron 112 CPs valle de 26 pacientes, con una edad promedio de 9,3 años. El 43,7% de las CPs correspondió a administración iv. Se obtuvieron más CPs ≥ 0,5 mg/L y ≥ 1,0 mg/L con la vía iv en relación a vo (p < 0,05). Pacientes bajo 12 años de edad recibieron mayor dosis en comparación a los ≥ 12 años (medianas 18,6 y 9,2 mg/kg/día, respectivamente, p < 0,05). La dosis vo más efectiva para alcanzar CPs ≥ 0,5 mg/L fue de 200 mg cada 12 h en todos los pacientes (80-100% de CPs ≥ 0,5 mg/L). En pacientes ≥ 12 años con dosis iv entre 14 y 20 mg/kg/día, 80% de las CPs fueron ≥ 1 mg/L y ≥ 2 mg/L. En pacientes bajo 12 años de edad, dosis entre 8-30 mg/ kg/día generaron similares resultados (50-63% para CPs ≥ 1 mg/L y 36-40% para CPs ≥ 2 mg/L). Ocho pacientes (30,8%), tuvieron alguna reacción adversa al fármaco, no encontrándose relación con la CP alcanzada. Conclusión: Una dosis estándar vo de 200 mg c/12 h de VCZ mostró los mejores resultados para profilaxis de AI en todos los pacientes. Pacientes bajo 12 años de edad requerirían dosis mayores a las utilizadas en este estudio para obtener CPs efectivas para tratamiento de AI. No se encontró relación entre CPs tóxicas y reacciones adversas.
Subject(s)
Humans , Male , Female , Child, Preschool , Child , Adolescent , Voriconazole/administration & dosage , Voriconazole/blood , Antifungal Agents/administration & dosage , Antifungal Agents/blood , Neoplasms/immunology , Aspergillosis/drug therapy , Reference Values , Administration, Oral , Retrospective Studies , Age Factors , Treatment Outcome , Drug Monitoring , Statistics, Nonparametric , Dose-Response Relationship, Drug , Pharmacovigilance , Immunocompetence/drug effects , Injections, Intravenous , Neoplasms/microbiologyABSTRACT
Objective To analyze the characteristics of serum vancomycin concentrations and its clinical therapeutic effects. Methods Serum vancomycin concentrations of 59 children diagnosed with severe Gram positive cocci pneumonia and treated with vancomycin were retrospectively analyzed. Vancomycin concentrations, biochemical values and disease status of patients were analyzed. Results The serum vancomycin concentrations of severe Gram positive cocci pneumonia children accompanied by acyanotic congenital heart disease was significantly higher than those without congenital heart disease, ( 12 . 12 mg/L vs 7 . 76 mg/L, P=0 . 008 ). The therapeutic effect of 40-60 mg/(kg·d) dosage group was signiifcantly higher than that of?60 mg/(kg·d) dosage group. Acute liver function damage and moderate/severe anemia may be risk factors for poor therapeutic effects to severe Gram positive cocci pneumonia children (P?
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Objective To establish a chemiluminescent immunoassay method for the determination of cathelicidin-BF (BF-30) in rat serum, to provide a fast and simple analytical method for its pharmacokinetic studies, then to investigate the pharmacokinetic characteristics of BF-30 in vivo. Methods A chemiluminescent immunoassay method was developed and the matrix effect, precision, accuracy, stability and the dilution effect were evaluated, then the method was used to determine the concentration of BF-30 in rat serum. Results The linear range of BF-30 in rat serum was 0.5-40 ng/ml, and the lowest limit of determination was 0.5 ng/ml. No matrix effect was observed. The RSD of inter-and intra-day precisions were 8.76%-14.15% and 4.91%-11.11%, respectively, and accuracy was-1.27%--7.71%. The stability of samples for 13 days and stock solution for 30 days at-20°C were good, and the stability of serum samples after 2 cycles of freeze-thaw met the requirements. There was no dilution effect noted after 40 times sample dilution. Conclusion We heve developed a simple, accurate and reliable method which can be applied to the determination of BF-30 in rat serum and following pharmacokinetic study.
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Objective To establish a determination method for valprate in serum .Methods Serum sample was acidified by sulfuric acid and extracted with ethyl ether ,cyclohexanecarboxylic acid was selected as an internal standard ,α-bromoaceto-phenone as derivative reagent .Determination was performed with HPLC with methanol :water (70:30) as the mobile phase . The nalytical column was Eclipse Plus C18 (150 mm × 4 .6 mm ,5 μm) ,detected at 248 nm ,the flow rate was 1 .0 ml/min .Re-sults The linear rang of valproate was 8 .65~173 μg/ml .The mean relative recovery was bigger than 99 .27% .Both the rela-tive standard deviation (RSD) of inter-day and intra-day was less than 5% .Conclusions The method is rapid ,accurate ,sensi-tive and suitable for clinical therapeutic drug monitoring .
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Objective To establish a method for the determination of quetiapine fumarate in human serum by RP‐HPLC and apply it into clinical .Methods Extracting with ethyl ether after serum‐drug was alkalized ,and then determined by RP‐HPLC .The determination was performed on Zorbax Eclipse XDB‐C18 column with mobile phase consisted of methanol‐water (70∶30 ,containing 0 .5% triethylamine and 0 .4% glacial acetic acid) at the flow rate of 0 .6 ml/min .The detection wave‐length was set at 254 nm ,and the column temperature was 35 ℃ .The method would be applied into analysis of clinical medica‐tion .Results Quetiapine fumarate and the impurities could be completely separated ,and the linear range of quetiapine fumar‐ate were 50‐1 000 ng/ml(r=0 .999 5) .The recovery of the method was 98 .2%‐100 .1% and the recovery of extracting was 75 .2%‐84 .6% .RSD of intra‐day was within 0 .8%‐3 .7% and RSD of inter‐day was within 1 .4%‐5 .1% .The limit of quantita‐tion for quetiapine fumarate was 2 .1 ng/ml .This method had been applied into clinical pharmacy and achieved a good effects . Conclusions The method is simple ,accurate ,reproducible ,and sensitive for determination of quetiapine fumarate in human se‐rum .It has important significance on instructing the rational use of clinical medicine and discovering the unreasonable drug combination .
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Objective To establish a chemiluminescent immunoassay method for the determination of cathelicidin-BF(BF-30)in rat serum,to provide a fast and simple analytical method for its pharmacokinetic studies,then to investigate the pharmacokinet?ic characteristics of BF-30 in vivo. Methods A chemiluminescent immunoassay method was developed and the matrix effect,preci?sion,accuracy,stability and the dilution effect were evaluated,then the method was used to determine the concentration of BF-30 in rat serum. Results The linear range of BF-30 in rat serum was 0.5-40 ng/ml,and the lowest limit of determination was 0.5 ng/ml. No matrix effect was observed. The RSD of inter-and intra-day precisions were 8.76%-14.15%and 4.91%-11.11%,respectively,and ac?curacy was-1.27%--7.71%. The stability of samples for 13 days and stock solution for 30 days at-20℃were good,and the stability of serum samples after 2 cycles of freeze-thaw met the requirements. There was no dilution effect noted after 40 times sample dilution. Conclusion We heve developed a simple,accurate and reliable method which can be applied to the determination of BF-30 in rat se?rum and following pharmacokinetic study.
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Tongmai granule (TM) is composed of Puerariae Lobatae Radix (Gegen), Salviae Miltiorrhizae Radix et Rhizoma(Danshen) and Chuanxiong Rhizoma(Chuanxiong). It has been used to treat ischemic cardio-cerebrovascular diseases for decades. For the purpose of elucidating its pharmacodynamic material foundation, the absorption and pharmacokinetic property of TM were investigated in acute myocardial ischemic model beagles. All serum samples were extracted before analysis with ethyl acetate after being acidified by hydrochloric acid. Under negative ESI detection mode, the chromatographic separation was carried out with monolithic C₁₈ column for gradient elution. A simultaneous quantitative analysis was made on 15 polyphenols, including 8 from Gegen, 5 from Danshen and 2 from Chuanxiong, in 8.5 min. The validation result demonstrated the specificity, accuracy and precision of the method in line with the bioanalysis requirements. After TM solution was administrated to acute myocardial ischemic model beagles through duodenum injection, serum samples were collected after 6 h. The quantitative detection proved the prompt absorption of TM, all of the components were detectable in the blood samples 5 min later, and reached peak respectively at 0.18-3.83 h after administration. The components presented large variabilities. The most components were exposed in serum with puerarin and salvianic acid A, followed by 3'-methoxypuerarin, mirificin, and 3'-hydroxypuerarin. The study proves puerarin and salvianic acid A are dominating active components of TM in acute myocardial ischemic model beagles.