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Objective:To conduct a retrospective analysis of efficacy and safety of different conversion schemes of tacrolimus to slow-release dosage forms for recipients in stable phase after renal transplantation to provide rationales for the conversion strategy of tacrolimus.Methods:From January 2020 to June 2020, clinical data were reviewed for 101 kidney transplant recipients converting from common tacrolimus dosage form to tacrolimus sustained-release dosage form during postoperative stable period.There were 62 males and 49 females with an age range of 19 to 69 years.They were divided into two groups according to iso-dose and incremental-dose switching schemes.The common dosage form of tacrolimus was converted into a sustained-release dosage form with different conversion doses, They were divided into two groups of 1∶1 conversion( n=55)and >1∶1 conversion( n=46). The clinical parameters of serum creatinine(Scr), blood urea nitrogen(BUN), alanine aminotransferase(ALT)and aspartate aminotransferase(AST), alkaline phosphatase(ALP), serum albumin(ALB), white blood cell count(WBC), urinary white blood cell(UWBC), hemoglobin(Hb)and fasting blood glucose(Glu)were compared between two groups after conversion. Results:Regarding numerical change trend after switching to tacrolimus sustained-release dosage form, drug dose/variation trend was smaller and blood drug concentration more stabilized.In two subgroups converted by 1∶1 and 1>1 initial dose, change trend of dose/blood concentration in 1∶1 conversion group appeared to be more stable.However, no inter-group difference existed in long-term parameters.Scr was lower at 1 week and 3 months after switching to extended-release dosage form( P<0.05)and BUN was lower at 2 weeks( P<0.05). In addition, at 5 months after conversion, ALT and AST significantly improved as compared with common dosage form( P<0.05). Significant differences existed in urinary WBC(UWBC)at 2/3 weeks( P<0.05). After switching for 2 weeks, hemoglobin significantly improved compared with common dosage form( P<0.05). No significant differences existed in ALP, ALB or Glu at other timepoints and pre-conversion( P>0.05). In 1∶1 switch group, renal function tended to improve.At 2 weeks, BUN was lower than pre-conversion; at 1/3 weeks, Scr was lower than pre-conversion( P<0.05). In addition, there was also a trend of improvement in liver function in 1∶1 conversion group.At 1 week and 5 months, ALT was lower than pre-conversion( P<0.05). However, no significant differences existed in AST, ALB, ALP, Glu, UWBC and serum WBC count at each timepoint between two different dose conversion groups( P>0.05). After conversion, intra-individual variability of tacrolimus trough concentration significantly improved( P<0.05). Conclusions:With the same safety and efficacy as common dosage form, sustained-release dosage form of tacrolimus may improve drug variability of individuals.When converting common dosage form into sustained-release dosage form, individual differences should be considered.While monitoring trough concentrations, proper doses should be adjusted on the basis of various clinical parameters.
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Objective:To improve the level of detection method and quality control at different transplant centers in China and comprehensively analyze the data of tacrolimus(Tac)detection in multiple transplant centers and provide data supports.Methods:Low, medium and high concentration commercial quality control products in triplicate samples were delivered to 34 domestic organ transplantation centers and testing repeated for 2~3 times during different time periods. The detection results of 240 quality control samples were summarized. The methods, accuracy and stability of Tac detection results were analyzed.Results:In international standard laboratories, mean±standard deviation(SD)of Tac detection results of low/medium/high concentration commercial quality control products was(4.70±0.325), (8.46±0.548)and(13.50±0.966)respectively. Here the results were (4.79±0.605), (8.49±0.948)and(13.99±1.604)respectively. In contrast, SD and degree of variation of international standard data were smaller, indicating that the accuracy and stability of international standard laboratories in detecting Tac were higher. SD of Tac concentrations detected by international standard laboratory for low/medium/high concentrations was approximately 0.3, 0.5 and 1.0 respectively, i.e.International first-class level. Here SD was approximately 0.5, 1.0 and 1.5 respectively, i.e. Chinese industry level.Conclusions:The "Chinese industry level" is recommended. Before using a new batch of "testing reagents" , "standard control samples" must be employed for calibrating the calculated curve. The calculated curve should be re-calibrated at least once per month. And clinicians should be consulted frequently.
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An on-line solid phase extraction-high performance liquid chromatography ( SPE-HPLC ) system was applied in the plasma pharmacokinetic study of highly active anti-cancer compound tyrosine kinase inhibitors (TEB-415) in mouse. The on-line SPE-HPLC method associated with Ultimate3000 system which was applied to the determination of the blood drug level of TEB-415 in mouse plasma. C18 column ( Venusil MP, 150 mm × 4. 6 mm, 5μm) was used as analytical column and the mobile phase consisted of acetonitrile-5 mmol/L monopotassium phosphate buffer ( pH 3 . 5 ) at a flow rate of 1 . 0 mL/min was used as the isocratic elution. An MF Ph-1 column (10 mm×4 mm, 5 μm) was used as on-line SPE column, and water and water-acetonitrile were used as the washing solvent and elution solvent respectively. The detection wavelength was set at 262 nm. The pharmacokinetic parameters were calculated by WinNonlin 5. 2 software. The linear range of the calibration curve was between 100 and 20000 μg/L, and the limit of qualification was 20 μg/L. The extraction recovery was between 90 . 5% and 94 . 6%. The RSD of intra-day and inter-day precision was less than 3. 5%. The accuracy of short-term stability, freeze-thaw stability and long-term stability were between 91. 49% and 101. 96%. After oral medication, the mean peak time (Tmax) of TEB-415 in mice was 5. 29 h, and the mean maximum concentration ( Cmax) was 3403μg/L. The area under the curve ( AUC) of TEB-415 was 24600 μg/L·h. This drug's mean half-life was 3. 84 h, and its mean retention time (MRT) was 6. 56 h. These parameters suggested that TEB-415 had appropriate rate of absorption and elimination with preferable bioavailability.
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Objective To determine diazepam, nitrazepam, oxazepam, estazolam, and al-prazolam simultaneously in human plasma by reversed phase high-performance liquid chromatography (RP-HPLC). Methods Ten microliter carbamazepine (50 mg/L)as the internal standard was added into 1 mL sample, which contained the 5 mixed sedative hypnotics as standard substance and human plasma as ground substance. They were extracted with acetoacetate from plasma samples, and then were dissolved by 100 μL mobile phase. The blood drug levels were analyzed by high perform-ance liquid chromatograph with 20 μL sample injection on a chromatographic column C 18 (4.6 mm×250 mm)at 30℃. The mobile phase consisted of methanol and water (65:35) , and the flow rate was 1.0 mL/min. The ultraviolet detection wavelength was 230 nm. Results The linearity range of the 5 drugs was 5～1 200 μg/L(r≥0.9966, P<0.05). The recovery rate was 95.5%～105.6%. The extraction recovery rate was more than 75%. The relative standard deviation (RSD) of intra-day and inter-day was less than 10% (n=5). Conclusion RP-HPLC method is convert-ient, accurate and sensitive for simultaneous determination of the concentration of diazepam, nitraze-pam, oxazepam, estazolam, and alprazolam in human plasma.
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AIM: To establish an LC-MS/MS method for determination of evodiamine concentration in rat plasma and to study its pharmacokinetic profile in rats. METHODS: Six rats were administrated (i.g.) evodiamine at the dose of 100 mg/kg. Blood samples were collected from eye socket. Evodiamine concentration in rat plasma was determined by LC-MS/MS method. The pharmacokinetic parameters were calculated using DAS program. RESULTS: A good linear relationship was obtained in the concentration range (0.2-50.0 ng/mL) studied (r2=0.9997). Average recoveries ranged from 96.12% to 99.46%. Intra-and inter-day relative standard deviations were 4.61%-13.51% and 5.65%-11.49%, respectively. The main pharmacokinetic parameters of evodiamine were as follows: Cmax (5.3±1.5) ng/mL; tmax (22±8) min; t1/2 (451±176) min. CONCLUSION: A selective and sensitive liquid chromatography-tandem mass spectrometric (LC-MS/MS) method for the quantification of evodiamine in rat plasma is developed and validated. This method is successfully applied for the pharmacokinetic studies of evodiamine in rats.
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The purpose of applying antibiotics prophylaxis in perioperative orthopedic surgery is to prevent or decrease the risk of infection.The opportune administration is the key point for prevention of infection.The application principle,classification and current situation are reviewed in this paper,its perspective and prospects are also investigated.
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OBJECTIVE:To detect the blood drug level of digoxin in order to offer reference about clinical safety and utility and rational use of cardiac glycoside drugs. METHODS: The plama concentration of digoxin was determined by fluorescence polarization immunization, and the monitoring rssults were subjected to statistical analysis. RESULTS: Of the total 126 cases who treated with digoxin, the blood drug concentration in 32(25.4%) was above 2.0 ng?mL-1,and it was 0.8～2.0 ng?mL-1 in 83(65.9%) and less than 0.8 ng?mL-1 in 11(8.7%); Toxic symptoms were noted in 16 cases(12.7%). CONCLUSION: To ensure clinical efficacy and reduce incidence of toxic reactions, it is of great importance to monitior the blood drug level and formulate individual dosage regimen.
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OBJECTIVE:To study the correlation between salivary drug concentration and blood,drug level its clinic sig-nificance.METHODS:The salivary drug concentration and blood drug level of gentamicin of15volunteer cases were deter-mined by radioimmunoassay.RESULTS:Both blood drug level and salivary drug concentration of gentamicin reached to peak level1hour after medication.CONCLUSION:The blood drug level of gentamicin and the salivary drug concentration of gentamicin are positively correlated,i.e.it is possible for salivary to substitute for blood in the therapeutic drug monitoring of gentamicin.
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Objective To explore the serum level of gentamycin for orally in children with serious illness.Methods The serum level of gentamycin in 41 children who were in serious illness [multiple organ dysfunction(MODS)group with 21 cases and non-MODS group with 20 cases ] were monitored and the patients were treated with select decontamination of the digestive tract(SDD) from October 2004 to April 2005.Dosage:10 mg/(kg?d),orally taken three times(every 8 hours) one day.The blood after taking the drug one hour later in the fourth day was selected and the serum level of getamycin was monitored.Results Thirty-six children of 41 cases serum level of gentamycin were negative and 5 children(4 in MODS group and 1 in non-MODS group) who had alimentary tract hemorrhage were masccline in serum after taking gentamycin one hour later in the forth day.The absorption of gentamycin from enteric after orally was not(rela)-ted to MODS.There were statistics value between the gestrintestinal tract ulcer and serum level of gentamycin.Conclusions The safety for treating the children in serious illness with gentamycin for SDD is obvious.But we suggest to monitor the serum level of gentamycin for who has severe alimentary tract hemorrhage together with insufficiency of liver and kindey.
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OBJECTIVE:To carry out individualized pharmotherapy and pharmaceutical care for patients.METHODS:With the aid of windows 98 operating platform,the Access 2000 database software was adopted to develop the patients'drug administration records on the basis of the results of the blood drug level monitoring and clinical information.RESULTS:The non-paper drug administration records built by Access had the advantages of convenient data process,huge information store,rapid inquiry system and so on.CONCLUSION:Access database software is worth recommending for clinical pharmacy and further studying.
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Objective To study the relationship between Lidocaine blood drug level and the cause of death from Lidocaine anaphylactic shock. Method Comparing and analyzing the blood drug levels by HPLC between two groups of people whose various indexes are normal before the surgery. Group 1 included 8 cases who accepted Lidocaine as anesthetic and died from Lidocaine anaphylactic shock. Group 2 included 11 cases who also took Lidocaine as anesthetic and passed the surgery smoothly. Results Lidocaine blood level of Group 1 (1.61?0. 45mg/L) is lower than that of Group 2 (2. 44 ?0. 47mg/L). Conclusion Lidocaine blood drug level has nothing to do with the cause of Lidocaine anaphylactic shock.