scholarly journals Therapeutic carbamazepine (CBZ) and valproic acid (VPA) monitoring in children using saliva as a biologic fluid

2008 ◽  
Vol 14 (2) ◽  
pp. 55-58 ◽  
Author(s):  
C. Maldonado ◽  
Pietro Fagiolino ◽  
M. Vázquez ◽  
A. Rey ◽  
I. Olano ◽  
...  
Keyword(s):  
Valproic Acid ◽  
Citric Acid ◽  
Therapeutic Drug Monitoring ◽  
Combined Therapy ◽  
Therapeutic Drug ◽  
Efflux Transporter ◽  
Drug Levels ◽  
Significant Difference ◽  
Daily Dose ◽  
Epileptic Children

OBJECTIVE: The aim of the study was to analyze retrospectively carbamazepine (CBZ) and valproic acid (VPA) salivary data collected from epileptic children during a 3-year period. METHODS: Saliva samples stimulated by citric acid were assayed by FPIA method. One hundred and three patients (aged 1-14 years) were in CBZ or VPA monotherapy or in CBZ-VPA combined therapy. RESULTS: VPA salivary levels were linearly related with daily dose, but a non-linear relationship was found for CBZ, in patients under monotherapy. VPA did not alter saliva CBZ concentration. Conversely, CBZ reduced VPA salivary levels. Non-responsive children displayed higher VPA concentrations. CBZ levels in uncontrolled patients showed non-significant difference in relation with controlled subjects even though their daily doses were higher. CONCLUSION: Citric acid stimulated saliva is reliable enough to perform therapeutic drug monitoring. Saliva drug levels in non-responsive patients would be explained according to the generalized efflux transporter overexpression hypothesis.

scholarly journals Isavuconazole Therapeutic Drug Monitoring during Long-Term Treatment for Chronic Pulmonary Aspergillosis

2020 ◽  
Vol 65 (1) ◽  
pp. e01511-20
Author(s):  
Chris Kosmidis ◽  
Akan Otu ◽  
Caroline B. Moore ◽  
Malcolm D. Richardson ◽  
Riina Rautemaa-Richardson
Keyword(s):  
Therapeutic Drug Monitoring ◽  
Adverse Events ◽  
Drug Monitoring ◽  
Therapeutic Drug ◽  
Pulmonary Aspergillosis ◽  
Drug Levels ◽  
Long Term Treatment ◽  
Daily Dose ◽  
Chronic Pulmonary Aspergillosis

ABSTRACTIsavuconazole is the newest triazole antifungal, and it displays a favorable pharmacokinetic and safety profile. Less is known about its long-term use in immunocompetent hosts. We performed a retrospective service evaluation of isavuconazole therapeutic drug monitoring in patients with chronic pulmonary aspergillosis. Adverse events (AEs) and dose adjustments made during routine clinical practice were recorded, and AEs were classified based on Common Terminology Criteria for Adverse Events v5.0. Forty-five patients (mean age, 64 years) had 285 isavuconazole blood drug levels measured (mean level, 4.1 mg/liter). A total of 117 measurements (41%) were performed on patients on a 100-mg daily dose instead of 200 mg, and all had blood levels of >1 mg/liter. Age (P = 0.012) and a daily dose of 200 mg versus 100 mg (P = 0.02) were independent predictors of levels of >6 mg/liter. AEs were recorded for 25 patients (56%). The mean drug level at the first measurement was 5.5 ± 2 mg/liter for patients reporting AEs, compared with 4.2 ± 1.7 mg/liter for those not reporting AEs (P = 0.032). The cutoff threshold best predictive of an AE was 4.6 mg/liter (area under the concentration-time curve, 0.710). Sixteen patients (36%) discontinued isavuconazole therapy due to AEs. Twenty-six patients (58%) continued on isavuconazole beyond 6 months. Asthma (P = 0.022) and a daily dose of 200 mg versus 100 mg (P = 0.048) were associated with AEs of grade 2 or higher. A reduced daily dose (100 mg versus 200 mg) of isavuconazole resulted in satisfactory drug levels in a substantial number of patients; it was better tolerated and enabled continuation of therapy for prolonged periods.

scholarly journals P152 Low rates of subtherapeutic drug levels are observed with proactive therapeutic drug monitoring of adalimumab

2021 ◽  
Author(s):  
Stephanie Shields ◽  
John Paul Seenan ◽  
Allan Dunlop ◽  
Peter Galloway ◽  
Jonathan Macdonald
Keyword(s):  
Therapeutic Drug Monitoring ◽  
Drug Monitoring ◽  
Therapeutic Drug ◽  
Drug Levels

scholarly journals High Blood Ammonia Levels Associated with Long-term Valproic Acids Therapy in Epileptic Children

2020 ◽  
Vol 4 (2) ◽  
pp. 83
Author(s):  
I Gusti Lanang Sidiartha ◽  
I Gusti Ngurah Made Suwarba ◽  
Dyah Kanya Wati ◽  
Ida Bagus Subanada
Keyword(s):  
Valproic Acid ◽  
Combination Therapy ◽  
Ammonia Level ◽  
Blood Ammonia ◽  
Cross Sectional ◽  
Acid Therapy ◽  
Blood Ammonia Level ◽  
Significant Difference ◽  
Epileptic Children

Background: Valproic acid is an effective drug for controlling seizure in children with epilepsy and it is usually used for treatment as long as two years or more. Blood ammonia level often increased in epileptic children who were treated with long-term valproic acid. The study was conducted to determine the relationship between blood ammonia level with valproic acid therapy in epileptic children.Materials and Methods: This is an observational study with cross-sectional approach. The subjects were 64 children with epilepsy, average age of 6.2 years old. Subjects were 33 boys and 31 girls. Blood ammonia level was examined using enzymatic glutamate dehydrogenase. Subjects were divided into 2 therapeutic groups based on the duration, doses and combination therapy of valproic acid. Subjects were recruited from Pediatric Neurology Clinic, Sanglah General Hospital, Bali, Indonesia, from May to December 2017. Comparison of blood ammonia level between groups were analyzed using an Independent t-test with significances if the p<0.05. Results: A significant difference of blood ammonia level was found between subjects who were treated with valproic acid less than 2 years and more than 2 years (45.7±16.4 mmol/L vs. 70.9±43.6 mmol/L; p=0.032). However, significant difference was not found between the groups according to the doses and combination therapy (p=0.450 and p=0.647, respectively).Conclusion: Blood ammonia level was significantly higher in epileptic children who used long-term valproic acid, hence it was recommended to check the blood ammonia level routinely.Keywords: ammonia, epilepsy, valproic, children

scholarly journals Therapeutic Drug Monitoring of Piperacillin-Tazobactam Using Spent Dialysate Effluent in Patients Receiving Continuous Venovenous Hemodialysis

2010 ◽  
Vol 55 (2) ◽  
pp. 557-560 ◽  
Author(s):  
Michael J. Connor ◽  
Charbel Salem ◽  
Seth R. Bauer ◽  
Christina L. Hofmann ◽  
Joseph Groszek ◽  
...  
Keyword(s):  
Therapeutic Drug Monitoring ◽  
Drug Monitoring ◽  
Kidney Injury ◽  
Therapeutic Drug ◽  
Plasma Drug ◽  
Drug Dosing ◽  
Drug Levels ◽  
Drug Concentrations ◽  
Continuous Venovenous Hemodialysis ◽  
Dosing Strategies

ABSTRACTSepsis and multisystem organ failure are common diagnoses affecting nearly three-quarters of a million Americans annually. Infection is the leading cause of death in acute kidney injury, and the majority of critically ill patients who receive continuous dialysis also receive antibiotics. Dialysis equipment and prescriptions have gradually changed over time, raising concern that current drug dosing recommendations in the literature may result in underdosing of antibiotics. Our research group directed its attention toward antibiotic dosing strategies in patients with acute renal failure (ARF), and we sought data confirming that patients receiving continuous dialysis and antibiotics actually were achieving therapeutic plasma drug levels during treatment. In the course of those investigations, we explored “fast-track” strategies to estimate plasma drug concentrations. As most antimicrobial antibiotics are small molecules and should pass freely through modern high-flux hemodialyzer filters, we hypothesized that continuous renal replacement therapy (CRRT) effluent could be used as the medium for drug concentration measurement by reverse-phase high-pressure liquid chromatography (HPLC). Here we present the first data demonstrating this approach for piperacillin-tazobactam. Paired blood and dialysate trough-peak-trough samples were drawn from 19 patients receiving piperacillin-tazobactam and continuous venovenous hemodialysis (CVVHD). Total, free, and dialysate drug concentrations were measured by HPLC. Dialysate drug levels predicted plasma free drug levels well (r2= 0.91 and 0.92 for piperacillin and tazobactam, respectively) in all patients. These data suggest a strategy for therapeutic drug monitoring that minimizes blood loss from phlebotomy and simplifies analytic procedures.

scholarly journals Predictors of Voriconazole Trough Concentrations in Patients with Child–Pugh Class C Cirrhosis: A Prospective Study

Antibiotics ◽  
2021 ◽  
Vol 10 (9) ◽  
pp. 1130
Author(s):  
Yichang Zhao ◽  
Jingjing Hou ◽  
Yiwen Xiao ◽  
Feng Wang ◽  
Bikui Zhang ◽  
...  
Keyword(s):  
Trough Concentration ◽  
Multiple Linear Regression Model ◽  
Therapeutic Drug ◽  
Time Activity ◽  
Bivariate Correlation ◽  
Significant Difference ◽  
Daily Dose ◽  
Pugh Class ◽  
Trough Concentrations ◽  
Class C

This prospective observational study aimed to clinically describe voriconazole administrations and trough concentrations in patients with Child–Pugh class C and to investigate the variability of trough concentration. A total of 144 voriconazole trough concentrations from 43 Child–Pugh class C patients were analyzed. The majority of patients (62.8%) received adjustments. The repeated measured trough concentration was higher than the first and final ones generally (median, 4.33 vs. 2.99, 3.90 mg/L). Eight patients with ideal initial concentrations later got supratherapeutic with no adjusted daily dose, implying accumulation. There was a significant difference in concentrations among the six groups by daily dose (p = 0.006). The bivariate correlation analysis showed that sex, CYP2C19 genotyping, daily dose, prothrombin time activity, international normalized ratio, platelet, and Model for end-stage liver disease score were significant factors for concentration. Subsequently, the first four factors mentioned above entered into a stepwise multiple linear regression model (variance inflation factor <5), implying that CYP2C19 testing makes sense for precision medicine of Child–Pugh class C cirrhosis patients. The equation fits well and explains the 34.8% variety of concentrations (R2 = 0.348). In conclusion, it needs more cautious administration clinically due to no recommendation for Child–Pugh class C patients in the medication label. The adjustment of the administration regimen should be mainly based on the results of repeated therapeutic drug monitoring.

scholarly journals Effect of sample heating on results of therapeutic drug monitoring

2021 ◽  
Vol 45 (3) ◽  
pp. 183-187
Author(s):  
Dao-Hai Cheng ◽  
Zhen-Guang Huang ◽  
Jing-Bing Zhu
Keyword(s):  
Heat Treatment ◽  
Valproic Acid ◽  
Therapeutic Drug Monitoring ◽  
Drug Monitoring ◽  
Whole Blood ◽  
Plasma Heating ◽  
Therapeutic Drug ◽  
Blood Concentrations ◽  
Therapeutic Drugs ◽  
Drug Concentrations

Abstract Objectives Heat treatment is a convenient measure for pathogens inactivation. The authors investigated the effects of this method on blood concentrations of six commonly therapeutic drugs. Methods Plasma and whole blood were pretreated with or without heating at 56 °C for 30 min, and drug concentrations of vancomycin, methotrexate, valproic acid, digoxin, carbamazepine, and cyclosporine were examined. Results Increased valproic acid levels after plasma heating (63.2 ± 30.2 vs. 62.1 ± 29.8 mg/L, mean recovery 102.0%) and whole blood heating (64.5 ± 30.5 vs. 62.1 ± 29.8 mg/L, mean recovery 104.6%) were observed (both p<0.05), but these differences were not considered clinically important. Recoveries of vancomycin in heat treatments varied widely, with an average and significant decrease of 15.8% in value after whole blood heating (11.7 ± 8.1 vs. 13.7 ± 8.6 mg/L, p<0.05). Conclusions Plasma or whole blood heating at 56 °C for 30 min are feasible in pathogens inactivation during monitoring methotrexate, valproic acid, digoxin, carbamazepine, and cyclosporine. However, such pretreatment seems inappropriate in monitoring vancomycin concentrations. Those results highlight the need for caution when applying heat treatment for pathogens inactivation in therapeutic drug monitoring.

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