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1.
Lupus Sci Med ; 9(1)2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-36328395

RESUMO

OBJECTIVE: Determine the pharmacokinetics (PK) and exposure-response of hydroxychloroquine (HCQ) and desethylhydroxychloroquine (DHCQ) in paediatric SLE (pSLE). METHODS: We conducted an exploratory phase 2, direct-to-family trial. Children enrolled in the Childhood Arthritis and Rheumatology Research Alliance (CARRA) Registry with a diagnosis of pSLE were eligible if they were receiving HCQ as standard of care for ≥3 months. Biological samples were collected at up to four visits over a 6-month period. At each visit, plasma was obtained to measure the concentrations of HCQ and DHCQ, as well as cytokines. HCQ and DHCQ plasma PK data were analysed using a population PK modelling approach. RESULTS: Twenty-five subjects provided a total of 88 plasma concentrations for PK analysis. There was a poor linear fit between HCQ concentrations and total body weight (R2=0.03). There was a decline in both interferon (IFN)-alpha and IFN-gamma with higher concentrations of HCQ and DHCQ. Volume of distribution for HCQ in plasma was higher in children compared with published values in adults (73 000 L vs 44 000 L), but clearance values in children were similar to adults. CONCLUSIONS: We report the first population PK model for HCQ and DHCQ in children using data from a novel direct-to-family clinical trial. We observed high interindividual variability in HCQ PK and found that weight-based dosing for HCQ is poorly correlated with drug concentrations, suggesting the need to use therapeutic drug monitoring to individualise dosing. Furthermore, our results suggest that the current weight-based dosing paradigm for HCQ may result in suboptimal drug exposures, particularly for children with obesity. Accordingly, additional studies of HCQ are needed in pSLE to determine the optimal drug concentration and dosing to reduce disease activity and improve outcomes. TRIAL REGISTRATION NUMBER: NCT04358302.


Assuntos
Antirreumáticos , Lúpus Eritematoso Sistêmico , Adulto , Criança , Humanos , Antirreumáticos/efeitos adversos , Monitoramento de Medicamentos/métodos , Hidroxicloroquina/uso terapêutico , Lúpus Eritematoso Sistêmico/tratamento farmacológico
2.
Ther Drug Monit ; 44(6): 777-783, 2022 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-36372935

RESUMO

BACKGROUND: Therapeutic drug monitoring (TDM) of ß-lactam antibiotics provides critical knowledge in hospital intensive care unit environments to support dosing within the narrow window between therapeutic failure and toxicity. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) is the most suitable analytical technique for these drugs; however, clinicians, patients, and laboratories would benefit from shortening the timeframe between the collection of samples and reporting of results. METHODS: The authors developed a very rapid LC-MS/MS method for 9 ß-lactam antimicrobial drugs on a commercial core-shell reverse-phase LC column by exploiting the performance of such stationary phase materials at a high mobile-phase linear velocity and using a simple flow split to optimize ionization conditions in the mass spectrometer ion source. The method's performance was assessed using a currently validated routine LC-MS/MS assay performed on the same instrument. RESULTS: Routine ß-lactam assays were reduced from >6 minutes per sample to less than 2 minutes with improved chromatographic resolution, while still maintaining acceptable analytical performance (average correlation coefficient: 0.99670, interday imprecision: 2.0%-10.8%, and bias: -1.68%), hence generating results in agreement with an existing validated method for patient and quality assurance program samples. CONCLUSIONS: Time-critical results, such as those for ß-lactam antimicrobials, may be reported by the TDM laboratory several hours earlier than current methods allow, providing improved patient care and generating capacity on LC-MS/MS instruments for larger batch sizes and/or additional assays. The simple-to-implement technique demonstrated in this study may be applicable to other TDM assays or any LC-MS/MS method where faster turnaround times are desirable.


Assuntos
Monitoramento de Medicamentos , Espectrometria de Massas em Tandem , Humanos , Antibacterianos/química , beta-Lactamas , Cromatografia Líquida de Alta Pressão/métodos , Cromatografia Líquida/métodos , Monitoramento de Medicamentos/métodos , Monobactamas , Reprodutibilidade dos Testes , Espectrometria de Massas em Tandem/métodos
3.
Pharmacol Res Perspect ; 10(6): e01026, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36398492

RESUMO

The most recent consensus guidelines for dosing and monitoring vancomycin recommended the use of area-under-the-curve with Bayesian estimation for therapeutic monitoring. As this is a modern concept in the practice of clinical pharmacy, the main objective of this review is to introduce the fundamentals of Bayesian estimation and its mathematical application as it relates to vancomycin therapeutic drug monitoring. In addition, we aim to identify pharmacokinetic (PK) software programs that incorporate Bayesian estimation for vancomycin dosing and to describe the PK models utilized in those software programs for the adult population. Twelve software programs that utilize Bayesian estimation were identified, which included: Adult and Pediatric Kinetics, Best Dose, ClinCalc, DoseMeRx, ID-ODS, InsightRx, MwPharm++, NextDose, PrecisePK, TDMx, Tucuxi, and VancoCalc. The software programs varied in the population PK models used as the Bayesian a priori. With the presence of various vancomycin Bayesian software programs, it is important to choose those that utilize PK models reflective of the specific patient population.


Assuntos
Farmácia , Vancomicina , Adulto , Humanos , Criança , Vancomicina/farmacocinética , Teorema de Bayes , Antibacterianos/uso terapêutico , Monitoramento de Medicamentos/métodos
4.
AAPS J ; 24(6): 117, 2022 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-36380020

RESUMO

Prior to his passing, Dr. Roger Jelliffe, expressed the need for educating future physicians and clinical pharmacists on the availability of computer-based tools to support dose optimization in patients in stable or unstable physiological states. His perspectives were to be captured in a commentary for the AAPS J with a focus on incorporating population pharmacokinetic (PK)/pharmacodynamic (PD) models that are designed to hit the therapeutic target with maximal precision. Unfortunately, knowing that he would be unable to complete this project, Dr. Jelliffe requested that a manuscript conveying his concerns be completed upon his passing. With this in mind, this final installment of the AAPS J theme issue titled "Alternative Perspectives for Evaluating Drug Exposure Characteristics in a Population - Avoiding Analysis Pitfalls and Pigeonholes" is an effort to honor Dr. Jelliffe's request, conveying his concerns and the need to incorporate modeling and simulation into the training of physicians and clinical pharmacists. Accordingly, Dr. Jelliffe's perspectives have been integrated with those of the other three co-authors on the following topics: the clinical utility of population PK models; the role of multiple model (MM) dosage regimens to identify an optimal dose for an individual; tools for determining dosing regimens in renal dialysis patients (or undergoing other therapies that modulate renal clearance); methods to analyze and track drug PK in acutely ill patients presenting with high inter-occasion variability; implementation of a 2-cycle approach to minimize the duration between blood samples taken to estimate the changing PK in an acutely ill patient and for the generation of therapeutic decisions in advance for each dosing cycle based on an analysis of the previous cycle; and the importance of expressing therapeutic drug monitoring results as 1/variance rather than as the coefficient of variation. Examples showcase why, irrespective of the overall approach, the combination of therapeutic drug monitoring and computer-informed precision dosing is indispensable for maximizing the likelihood of achieving the target drug concentrations in the individual patient.


Assuntos
Monitoramento de Medicamentos , Assistência ao Paciente , Masculino , Humanos , Monitoramento de Medicamentos/métodos , Simulação por Computador
5.
Orphanet J Rare Dis ; 17(1): 400, 2022 11 03.
Artigo em Inglês | MEDLINE | ID: mdl-36329442

RESUMO

BACKGROUND: To date, measurement of intracellular cystine is used for the therapeutic monitoring of patients affected by cystinosis in treatment with cysteamine. Since this method is time and sample consuming, development of a faster method to quantify cysteamine would be extremely useful in order to help clinicians to adjust dosages of cysteamine and to define better the pharmacokinetic profile of this drug. The aim of the study was to develop a liquid chromatography tandem mass spectrometry method for the quantification of cysteamine in plasma samples and to test its applicability on plasma samples derived from patients with nephropathic infantile cystinosis in treatment with cysteamine. RESULTS: The percentage of accuracy of the developed method varied between 97.80 and 106.00% and CV% between 0.90 and 6.93%. There was no carry over. The calibration curves were built from 2.5 to 50 µM. The limit of detection and the lower limit of quantification occurred at 0.25 and 1.25 µM respectively. Cysteamine was stable up to 2 months at -20 °C. Concentrations of cysteamine and intracellular cystine of 4 patients were in line with data previously reported. CONCLUSION: The proposed method showed an appropriate selectivity, specificity, linearity, sensibility, accuracy, precision and good applicability to samples.


Assuntos
Cistinose , Humanos , Cistinose/tratamento farmacológico , Cistinose/diagnóstico , Cisteamina/uso terapêutico , Cisteamina/efeitos adversos , Cistina/análise , Cistina/uso terapêutico , Monitoramento de Medicamentos
6.
Analyst ; 147(23): 5445-5454, 2022 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-36317701

RESUMO

Dried blood spot(s) (DBS) microsampling has increasingly attracted interest as a patient-centric alternative to conventional blood withdrawal. Despite the many advantages associated with DBS sampling, its widespread use in clinical practice is still hampered, which is mainly caused by the hematocrit (Hct) effect. One approach to cope with this issue is the Hct prediction of DBS using ultraviolet-visible (UV-Vis) spectroscopy. Recently, a UV-Vis-based Hct prediction module has been incorporated into the automated CAMAG® DBS-MS 500 HCT system. However, although a proof-of-principle yielded promising results, there is no formal in-depth evaluation of the performance of this module. Hence, it remained to be established to what extent automated Hct prediction of DBS via this module can universally be applied and generates acceptable results. Using authentic patient samples, we set up and validated a calibration model and evaluated whether this could serve as a 'generic' calibration model for different, independent Hct prediction modules. A quadratic calibration curve with 1/x2 weighting was established. The bias, intra-day and total precision were below 0.025 L L-1, 2.2% and 2.7%, respectively. Additionally, the influence of storage and the robustness of the method was evaluated. Moreover, a lab-lab comparison of the performance of the Hct module of two independently operated instruments demonstrated that the validated model can be used as a generic calibration model. Finally, application of the method to venous DBS (n = 48) prepared from patient samples in the context of therapeutic drug monitoring of tacrolimus revealed a good concordance between the actual (i.e. Sysmex-based) and UV-Vis-based predicted Hct.


Assuntos
Teste em Amostras de Sangue Seco , Monitoramento de Medicamentos , Humanos , Hematócrito , Teste em Amostras de Sangue Seco/métodos , Calibragem , Análise Espectral
7.
Medicine (Baltimore) ; 101(38): e30683, 2022 Sep 23.
Artigo em Inglês | MEDLINE | ID: mdl-36197194

RESUMO

Therapeutic drug monitoring (TDM) is effective in optimizing the efficacy of infliximab in patients with inflammatory bowel disease (IBD). An affordable way of monitoring is in high demand. This study evaluated the analytical and clinical performances of the newly available Remsima monitor kits and compared them with the established enzyme-linked immunosorbent assay kits. The trough level of infliximab in patients with IBD treated with an infliximab originator (Remicade) or biosimilar compounds (Remsima and Remaloce) was measured using a Remsima® Monitor Drug Level (Remsima) kit at the Samsung Medical Center, Seoul, Korea. Twenty-six plasma samples were collected immediately before the infusion of infliximab from 18 patients with IBD (Remicade, n = 8; Remsima, n = 6; and Remaloce, n = 4). The intra-assay intraclass correlation coefficient (ICC) of the RIDA and Remsima kits was 0.951 (95% CI = 0.908-0.976) and 0.990 (95% CI = 0.981-0.995). The inter-assay ICC of infliximab trough level between the RIDA and Remsima kits was very high (R = 0.971; 95% CI = 0.935-0.987), and the mean difference between the kits was 1.458 (95% limits of agreement = -3.302 to 6.219). The intra- and inter-assay reliabilities of all types of infliximab did not show significant differences. Qualitative stratification revealed substantial similarities between the kits (weighted kappa = 0.798). This study indicated that the Remsima kit was reproducible and highly correlated with the RIDA kit.


Assuntos
Medicamentos Biossimilares , Doenças Inflamatórias Intestinais , Scrapie , Animais , Anticorpos Monoclonais , Medicamentos Biossimilares/uso terapêutico , Monitoramento de Medicamentos , Fármacos Gastrointestinais/uso terapêutico , Humanos , Doenças Inflamatórias Intestinais/tratamento farmacológico , Infliximab , Scrapie/tratamento farmacológico , Ovinos
8.
Adv Clin Chem ; 110: 73-116, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36210077

RESUMO

Although the measurement of aminoglycosides and glycopeptides in blood has been well established, it has become evident that therapeutic drug monitoring (TDM) should be extended to other antibiotics such as beta-lactams, daptomycin and linezolid. The use of a TDM guided approach allows reliable assessment of target concentration thus mitigating the risk for toxicity and preventing antibiotic resistance. This is especially relevant for the critically ill in intensive care. Herein we provide an overview on the different antibacterial antibiotics and their target pharmacokinetic/pharmacodynamic indexes in general as well as the importance for TDM of antibacterial antibiotics specifically. Analytical methods applicable to this approach in clinical laboratories are explored and highlighted.


Assuntos
Antibacterianos , Daptomicina , Aminoglicosídeos , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Daptomicina/farmacologia , Daptomicina/uso terapêutico , Monitoramento de Medicamentos/métodos , Glicopeptídeos/farmacologia , Humanos , Linezolida/farmacologia , Linezolida/uso terapêutico , beta-Lactamas/farmacologia , beta-Lactamas/uso terapêutico
9.
Int J Mol Sci ; 23(19)2022 Sep 23.
Artigo em Inglês | MEDLINE | ID: mdl-36232517

RESUMO

Current guidelines recommend monitoring the anticoagulant effect of unfractionated heparin (UFH) by measuring anti-Xa activity rather than activated partial thromboplastin time (aPTT) in intensive care unit (ICU) patients. The primary objective of this study was to evaluate the correlation of aPTT, anti-Xa activity, and thrombin generation in UFH-treated ICU patients. A prospective observational pilot study was conducted in adult surgical ICU patients treated with UFH. aPTT and anti-Xa activity were monitored daily. The therapeutic target was aPTT between 50 s and 84 s, and/or anti-Xa between 0.3 and 0.7 U/mL. Correlation among aPTT, anti-Xa activity, and thrombin generation was determined by measuring endogenous thrombin potential (ETP), with the inflammatory response evaluated. C-reactive protein (CRP) was used as a marker of inflammatory response. The plasma of 107 samples from 30 ICU patients was analyzed. The correlation between aPTT and anti-Xa activity was 0.66, CI95% [0.54;0.76] (p < 0.0001). Although thrombin generation, aPTT, and anti-Xa were correlated with inflammatory responses, the correlation was higher with thrombin generation and anti-Xa activity compared to aPTT. When aPTT was in a therapeutic range, a low thrombin generation was observed but was 50% inhibited when anti-Xa was in a therapeutic range. Coagulation testing with aPTT, anti-Xa correlated with thrombin generation. A 50% decrease in thrombin generation was observed when anti-Xa was within a therapeutic range. Further work is needed to evaluate coagulation biomarker responses and clinical outcomes in specific ICU populations.


Assuntos
Heparina , Trombina , Adulto , Anticoagulantes/farmacologia , Anticoagulantes/uso terapêutico , Biomarcadores , Proteína C-Reativa , Monitoramento de Medicamentos , Inibidores do Fator Xa/farmacologia , Inibidores do Fator Xa/uso terapêutico , Heparina/farmacologia , Heparina de Baixo Peso Molecular , Humanos , Unidades de Terapia Intensiva , Tempo de Tromboplastina Parcial , Estudos Prospectivos
10.
Biomed Pharmacother ; 155: 113777, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36271558

RESUMO

BACKGROUND: The revised vancomycin guidelines recommend replacing trough-only with trough or peak/trough Bayesian and first-order equations monitoring, citing their better AUC predictions and poor AUC-trough R2. Yet, evidence suggesting good AUC-trough correlation has been overlooked, and the optimality of peak/trough samples has been doubted. The guidelines recommend Bayesian programs implement richly-sampled PopPK priors despite their scarcity. Therefore, whether complex Bayesian and sample-demanding first-order equations can bring significant advantages to the practice over simple trough-only monitoring is worth weighing. OBJECTIVES: The primary aim is to compare the predictive performance of the AUC monitoring methods. Then, we investigate the impact of not adhering to trough sampling on the Bayesian-based predictions. Moreover, we report the nature of PopPK priors used in Bayesian programs to assess the applicability of the guideline recommendations. METHODS: We calculated the predictive performance of the monitoring methods using a standard PopPK modeling and simulation approach. We thoroughly explored the prior PK models implemented in Bayesian programs. RESULTS: Predictive performances of the monitoring methods were comparable at steady-state relative to the number of samples. Contrary to the recommendation, Bayesian trough monitoring did not result in better predictive performances compared to using random levels. Very few programs implemented richly-sampled priors. CONCLUSION: All the monitoring methods can be, relatively, reliable at steady-state, if properly implemented. Although only Bayesian-based monitoring can be used pre-steady-state, its predictive performance can be modest. Trough-only monitoring is the simplest approach. Constraints regarding trough sampling times could be relaxed. The scarcity of richly-sampled Bayesian priors questions the applicability of the revised guidelines recommendation.


Assuntos
Monitoramento de Medicamentos , Vancomicina , Monitoramento de Medicamentos/métodos , Teorema de Bayes , Área Sob a Curva , Antibacterianos/uso terapêutico , Testes de Sensibilidade Microbiana
11.
Artigo em Inglês | MEDLINE | ID: mdl-36244237

RESUMO

Therapeutic drug monitoring (TDM) of antibiotics (ATB) in patients with serious bacterial infections allows optimization of the efficacy of the treatment while reducing the risk of toxicity. Notably, early measurement of plasma beta-lactam concentration has been shown to be associated with reduced mortality in intensive care patients. In this context, a rapid, robust, and accurate assay method is essential for daily TDM. A fully automated procedure for quantification of the plasma concentrations of ten ATB was developed. The ATB were divided into two calibration pools, with Pool 1: aztreonam, ceftobiprole, cefoxitin, avibactam, tazobactam and Pool 2: metronidazole, ceftriaxone, daptomycin, ceftolozane, moxifloxacin. Sample preparation consisting of acetonitrile plasma protein precipitation and H20 dilution was applied to all analytes. This procedure was carried out by an automated sample preparation system directly coupled to a liquid chromatography-tandem mass spectrometry (LC-MS/MS) system. Since the instrument extracts sample n while sample n-1 is in the LC-MS/MS system, the delay between obtaining the results for two samples corresponds to the analytical run time, which is less than 7 min. The method was validated according to the Food and Drug Administration guidelines. The method was sensitive (lower limit of quantification 0.1-1 mg/L, depending on the ATB), accurate (intra/inter-assay bias -14.8 to 14.2 %) and precise (intra/inter-assay CVs 1.27 to 16.3 %). Application of the TDM assay was illustrated by the report of an intensive care patient treated with the ceftazidime/aztreonam/avibactam combination. Four assays were performed in 8 days with results returned within 24 h to quickly manage the dose regimen in this patient. An automated, simple, rapid, robust LC-MS/MS analysis was developed and validated for the simultaneous quantification of plasma concentrations of 10 ATB and was applied with success to perform TDM. This method provides a shorter turnaround time than classic sample batch-based analytical methods.


Assuntos
Antibacterianos , Espectrometria de Massas em Tandem , Humanos , Cromatografia Líquida de Alta Pressão/métodos , Espectrometria de Massas em Tandem/métodos , Cromatografia Líquida/métodos , Aztreonam , Monitoramento de Medicamentos/métodos , Reprodutibilidade dos Testes
12.
Anal Biochem ; 659: 114951, 2022 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-36244510

RESUMO

A rapid back flushed (BF) direct sample injection (DSI) high-performance liquid chromatography (HPLC) with UV detection (BF-DSI-HPLC-UV) has been developed to determine terbinafine (TERB) in human serum. For online solid phase extraction step, an isocratic mobile phase of phosphate buffer saline (pH 7.4) at 1 mL/min and a short protein-coated ODS column (PC-ODS-column) were used for the purification and enrichment of TERB. Two different chromatographic modes of PC-ODS-column were simultaneously operated. Macromolecular proteins were extracted by size-exclusion liquid chromatography, while TERB trapping and enrichment were achieved through reversed-phase liquid chromatography. The clear fraction containing TERB was transferred from the PC-ODS-column by BF mode onto the quantification step through a high pressure switching valve. An analytical mobile phase consisting of 80% methanol and 1% triethylamine in distilled deionized water (pH) 6 at 1 mL/min was used for the final separation on an ODS analytical column. TERB was quantified and detected by UV-detector at 224 nm. The proposed method showed high correlation coefficient (>0.999) over the concentrations range 4-1600 ng/mL with recoveries ranging from 98.48 to 93.86%. Measurement of TERB concentration in serum after administration of a single dose of 250 mg oral tablet was used to evaluate the applicability of the BF-DSI-HPLC-UV for pharmacokinetic study.


Assuntos
Monitoramento de Medicamentos , Extração em Fase Sólida , Humanos , Cromatografia Líquida de Alta Pressão/métodos , Terbinafina , Cromatografia em Gel , Indicadores e Reagentes , Reprodutibilidade dos Testes
13.
Biomed Pharmacother ; 156: 113899, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36279720

RESUMO

Cannabinoid derivates have been largely used for different medical purpose. In the literature, several methods capable of separating THC and its principles metabolites are described, although Δ8- and Δ9-THC separation has not been completely achieved. THC metabolism has not been fully understood and metabolites plasma distribution in healthy and pathological patients remains to further deepen. The aim of this study was the validation of UHPLC-MS/MS method for the quantification of 10 cannabinoids in human plasma, as important tool for improving clinical efficacy of cannabis administration. Obtained results were in accordance with recommendations of ICH Harmonised Guideline for bioanalytical method validation, showing a good linearity, optimal accuracy as well as satisfactory results in terms of intra-day and inter-day precision and matrix effect. Furthermore, blood sampling study was performed to investigate the better collection method. Optimal separation of Δ-9-tetrahydrocannabinol (Δ9-THC), Δ8-tetrahydrocannabinol (Δ8-THC) was obtained. The present method showed optimal linearity and satisfactory results in terms of specificity and selectivity. Recovery was between 92.0% and 96.5% for all analytes. The matrix-effect showed good performance; no carry over was observed. Cannabinoid metabolites present in higher plasma concentrations were: 11-Hydroxy-Δ9-tetrahydrocannabinol, 11-Nor-9carboxy-Δ9-tetrahydrocannabinol and THC-COOH-glucuronide. Method performance makes it suitable for routine purposes and a potential tool for therapeutic ranges definition. The present work will be used to test several samples in a long-term clinical study, paving the way for further future works.


Assuntos
Canabinoides , Espectrometria de Massas em Tandem , Humanos , Espectrometria de Massas em Tandem/métodos , Canabinoides/metabolismo , Dronabinol/metabolismo , Cromatografia Líquida de Alta Pressão/métodos , Monitoramento de Medicamentos
14.
Per Med ; 19(6): 509-521, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36285598

RESUMO

Aim: To assess pharmacists' and physicians' knowledge, attitudes and practices toward therapeutic drug monitoring (TDM) service at the Children's Cancer Hospital Egypt 57357. Materials & methods: This was a single-site cross-sectional study where all practicing pharmacists and physicians were eligible to participate. Results: A statistically significant difference in the knowledge scores between pharmacists and physicians (p = 0.022) was found. In general, attitudes toward TDM among pharmacists and physicians were positive. Regarding practices, pharmacists were more likely than physicians to agree or strongly agree that they have studied some scientific references on TDM (p = 0.034), but more physicians recommend the TDM service (p = 0.046). Conclusion: A multidisciplinary educational program in Egypt for TDM for both medicine and pharmacy staff will improve interprofessional collaboration in the clinical setting, leading to better personalized medication management.


The objective of the present survey was to evaluate the knowledge, attitudes and practices of pharmacists and physicians toward therapeutic drug monitoring (TDM) services at the Children's Cancer Hospital Egypt 57357. TDM is defined as 'measuring the amount of specific drugs in patients' blood to ensure that the concentrations of administered drugs are both effective and safe'. A single-centered study was conducted at the CCHE where all pharmacists and physicians participated. There was a remarkable difference in the knowledge scores between pharmacists and physicians. Generally, both pharmacists and physicians demonstrated positive attitudes toward TDM. In real-life practice, pharmacists were more likely than physicians to agree that they had scientific evidence about TDM. Multidisciplinary educational programs for TDM among physicians and pharmacists would improve interprofessional collaboration for the benefit of patients in Egypt.


Assuntos
Atitude do Pessoal de Saúde , Conhecimentos, Atitudes e Prática em Saúde , Criança , Humanos , Egito , Estudos Transversais , Monitoramento de Medicamentos , Medicina de Precisão , Comportamento Cooperativo
15.
Med Oncol ; 39(12): 259, 2022 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-36224276

RESUMO

The favorable outcomes of venetoclax-based regimens in older adults with acute myeloid leukemia (AML) may result in its regimen becoming the standard treatment. However, the dosage of venetoclax is fixed, irrespective of body surface area (BSA) or weight. Therefore, individualized dosing using therapeutic drug monitoring (TDM) may help optimize treatment in a safe and effective manner. Twelve patients with AML who received venetoclax-based treatment were enrolled in this study. Blood samples were collected before venetoclax administration, and the minimum plasma concentration (Cmin) was evaluated. The concentration of venetoclax was evaluated using a simple, sensitive, and cost-effective assay using high-performance liquid chromatography, as described previously. The median age was 74 (70-85) years. Ten patients received venetoclax in combination with azacitidine and one patient received low-dose cytarabine (LDAC). The patients BSA ranged from 1.345 to 1.912 m2 (median 1.543). The dose of venetoclax was 400 mg with azacitidine, and 600 mg with LDAC. In four patients who were taking CYP3A4 inhibitors, venetoclax was reduced to 50 mg according to the prescribing information. The Cmin ranged from 0.39 to 2.49, and the patient taking itraconazole showed highest Cmin regardless of the reduction of venetoclax. Most patients showed higher Cmin compared to the data from previous clinical trials, and BSA and venetoclax concentrations showed a negative correlation. Many Asian AML patients > 75 years old are petite and receive CYP3A4 inhibitors. Therefore, the TDM of venetoclax may be useful.


Assuntos
Monitoramento de Medicamentos , Leucemia Mieloide Aguda , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Azacitidina/uso terapêutico , Compostos Bicíclicos Heterocíclicos com Pontes/efeitos adversos , Citarabina , Inibidores do Citocromo P-450 CYP3A/uso terapêutico , Humanos , Itraconazol , Leucemia Mieloide Aguda/induzido quimicamente , Sulfonamidas
17.
Cancer ; 128(22): 3951-3958, 2022 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-36181667

RESUMO

BACKGROUND: Imatinib treatment often produces various adverse reactions in patients with chronic myeloid leukemia (CML), and increasing patients are pursuing dose optimization. In this study, the authors aimed to explore imatinib dose optimization based on therapeutic drug monitoring (TDM) in CML patients. METHODS: The relationship between imatinib concentration and clinical response and adverse reactions was evaluated, then the dose-reduction data in 110 Chinese CML patients was also explored. RESULTS: Patients with a major molecular response (MMR) had higher imatinib plasma concentration compared with those not achieving MMR (1473.70 ± 419.13 vs. 985.8 ± 213.32 ng/ml) when receiving 400 mg daily. Imatinib concentration >1000 ng/ml predicted improved event-free survival and failure-free survival. In addition, imatinib concentration was significantly correlated with leukopenia or neutropenia, diarrhea, edema, and rash. Patients receiving imatinib concentration >1685 ng/ml were more susceptible to diarrhea and those with levels >1575 ng/ml were more susceptible to periorbital and limb edema. Thirty-nine (35.5%) patients underwent low-dose therapy and seven (6.4%) patients received discontinuation therapy. Patients with a higher imatinib concentration were more likely to maintain MMR or deep molecular response after dose reduction. No significant difference in molecular relapse-free survival rate was observed between the low-dose and standard-dose groups over 1 year and 2 years. Furthermore, most adverse reactions significantly improved after dose reduction. CONCLUSIONS: Imatinib concentration was closely associated with clinical response and adverse reactions, suggesting that dose optimization based on TDM might achieve beneficial clinical outcomes. Dose reduction based on TDM is feasible and safe for patients exhibiting optimal response, which could improve adverse reactions.


Assuntos
Antineoplásicos , Leucemia Mielogênica Crônica BCR-ABL Positiva , Leucemia Mieloide de Fase Crônica , Humanos , Mesilato de Imatinib/uso terapêutico , Monitoramento de Medicamentos , Pirimidinas/uso terapêutico , Benzamidas , Piperazinas/uso terapêutico , Antineoplásicos/uso terapêutico , Leucemia Mieloide de Fase Crônica/tratamento farmacológico , Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológico , Diarreia/induzido quimicamente , China
19.
J Clin Psychopharmacol ; 42(6): 552-559, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36286707

RESUMO

BACKGROUND: Olanzapine (OLA) is an atypical second-generation antipsychotic that exhibits significant pharmacokinetic variability. We retrospectively investigated the effects of age, sex, and specific comedications on OLA pharmacokinetics in Chinese patients with schizophrenia. METHODS: Data on sex, age, and OLA dosage and steady-state plasma concentrations of 386 patients with schizophrenia (who have received OLA or a comedication of OLA with a psychotherapeutic drug) were collected and analyzed. The combined effects of dosage, age, sex, and comedication on OLA plasma levels were assessed via multiple linear regression analyses. RESULTS: A daily dose of OLA was positively correlated with the drug's plasma concentrations. Overall, the OLA plasma concentrations and concentration-to-dose ratio (C/D) of the studied patients varied by 53.6- and 64.1-fold, achieving median values of 42.7 ng/mL and 2.73 (ng/mL)/(mg/d), respectively. Furthermore, a 1.27-fold higher estimated C/D in patients 60 years or older than in those younger than 60 years was identified. Female patients demonstrated a 33.6% higher C/D than in male patients. When coadministered with mood stabilizers (valproate or lithium), the median OLA C/D was 24.1% to 26.1% lower than that of OLA monotherapy. Interestingly, the OLA plasma concentration and C/D were not significantly affected by a comedication with aripiprazole, haloperidol, amisulpride, risperidone, clozapine, ziprasidone, citalopram, or buspirone. CONCLUSIONS: The administered drug's dose was identified as an important determinant of the achieved OLA plasma concentration, with a positive correlation. The patients' sex and valproate (or lithium) comedication can significantly affect the C/D of OLA. Therapeutic drug monitoring should be routinely applied in cases of OLA-receiving patients with schizophrenia.


Assuntos
Antipsicóticos , Esquizofrenia , Humanos , Masculino , Feminino , Olanzapina/uso terapêutico , Esquizofrenia/tratamento farmacológico , Monitoramento de Medicamentos , Lítio/uso terapêutico , Ácido Valproico/uso terapêutico , Estudos Retrospectivos , Benzodiazepinas , China
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