scholarly journals The influence of CYP2C8*3 on carbamazepine serum concentration in epileptic pediatric patients

2016 ◽  
Vol 19 (1) ◽  
pp. 21-28 ◽  
Author(s):  
DD Milovanovic ◽  
JR Milovanovic ◽  
M Radovanovic ◽  
I Radosavljevic ◽  
S Obradovic ◽  
...  
Keyword(s):  
Serum Concentration ◽  
High Performance ◽  
Dose Adjustment ◽  
Pediatric Patients ◽  
Plasma Concentrations ◽  
Clinical Importance ◽  
Population Pharmacokinetic Analysis ◽  
Pharmacokinetic Analysis ◽  
Population Pharmacokinetic ◽  
Allele Specific

AbstractThe aim of the present study was to investigate the distribution of CYP2C8 variants *3 and *5, as well as their effect on carbamazepine pharmacokinetic properties, in 40 epileptic pediatric patients on carbamazepine treatment. Genotyping was conducted using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP), and allele-specific (AS)-PCR methods, and steady-state carbamazepine plasma concentrations were determined by high performance liquid chromatography (HPLC). The CYP2C8 *3 and *5 polymorphisms were found at frequencies of 17.5 and 0.0%, respectively. After dose adjustment, there was a difference in daily dose in CYP2C8*3 carriers compared to non carriers [mean ± standard deviation (SD): 14.19 ± 5.39 vs. 15.46 ± 4.35 mg/kg; p = 0.5]. Dose-normalized serum concentration of carbamazepine was higher in CYP2C8*3 (mean ± SD: 0.54 ± 0.18 vs. 0.43 ± 0.11 mg/mL, p = 0.04), and the observed correlation between weight-adjusted carbamazepine dose and carbamazepine concentration after dose adjustment was significant only in CYP2C8*3 non carriers (r = 0.52, p = 0.002). However, the population pharmacokinetic analysis failed to demonstrate any significant effect of CYP2C8 *3 polymorphism on carbamazepine clearance [CL L/h = 0.215 + 0.0696*SEX+ 0.000183*DD]. The results indicated that the CYP2C8*3 polymorphism might not be of clinical importance for epilepsy treatment in pediatric populations.

scholarly journals O02 Developmental pharmacogenetics of SLCO2B1 on montelukast pharmacokinetics in chinese children

2019 ◽  
Vol 104 (6) ◽  
pp. e1.2-e1
Author(s):  
Q Li ◽  
K Wang ◽  
H-Y Shi ◽  
Wu Y-E ◽  
Y Zhou ◽  
...  
Keyword(s):  
High Performance ◽  
Plasma Concentrations ◽  
Population Pharmacokinetic Analysis ◽  
Individual Variability ◽  
Chinese Children ◽  
Pharmacokinetic Analysis ◽  
Population Pharmacokinetic ◽  
Pharmacokinetic Studies ◽  
Fluorescence Detector ◽  
Nonlinear Mixed Effects Model

BackgroundMontelukast, a potent orally selective leukotriene-receptor antagonist, inhibits the action of cysteinyl-leukotriene in patients with asthma.Although pharmacokinetic studies of montelukast have been reported in Caucasian adults and children, and showed significant inter-individual variability on pharmacokinetics.None of pharmacokinetic study has been explored in Chinese children. Given the potential inter-ethnic difference, the purpose of this study was to evaluate the effects of developmental factors and pharmacogenetics of CYP2C8 and SLCO2B1on Montelukast pharmacokinetics in Chinese paediatric patients.MethodsAfter oral administration with montelukast, opportunistic samples were collected from asthma children and plasma concentrations were determined by high performance liquid chromatography coupled with fluorescence detector (HPLC-FLD) method. Population pharmacokinetic analysis was performed using a nonlinear mixed-effects model approach (NONMEM V 7.2.0) and variants of CYP2C8 and SLCO2B1 were genotyped.ResultsFifty patients (age range 0.7–10.0 years) with asthma were enrolled in this study. The clearance of montelukast was significantly higher in subjects with SLCO2B1 c.935GA and c.935AAgenotype compared withSLCO2B1 c.935GGsubjects (0.94±0.26 versus 0.77±0.21, p=0.020). Weight was also found to be significantly corrected with montelukast clearance (p 0.0001).ConclusionsThe developmental pharmacogenetics of montelukast in Chinese children was evaluated. Weight and SLCO2B1 genotype showed independently significant impacts on theclearanceofmontelukast.Disclosure(s)Nothing to disclose.

scholarly journals A Population Pharmacokinetic Analysis of Milrinone in Pediatric Patients After Cardiac Surgery

2004 ◽  
Vol 31 (1) ◽  
pp. 43-59 ◽  
Author(s):  
James M. Bailey ◽  
Timothy M. Hoffman ◽  
David L. Wessel ◽  
David P. Nelson ◽  
Andrew M. Atz ◽  
...  
Keyword(s):  
Cardiac Surgery ◽  
Pediatric Patients ◽  
Population Pharmacokinetic Analysis ◽  
Pharmacokinetic Analysis ◽  
Population Pharmacokinetic

scholarly journals Interventional cohort study of prolonged use (>72 hours) of paracetamol in neonates: protocol of the PARASHUTE study

2019 ◽  
Vol 3 (1) ◽  
pp. e000427 ◽  
Author(s):  
Sissel Sundell Haslund-Krog ◽  
Steen Hertel ◽  
Kim Dalhoff ◽  
Susanne Poulsen ◽  
Ulla Christensen ◽  
...  
Keyword(s):  
Cohort Study ◽  
Neonatal Intensive Care ◽  
Plasma Concentrations ◽  
Population Pharmacokinetic Analysis ◽  
Pharmacokinetic Analysis ◽  
Population Pharmacokinetic ◽  
Concomitant Treatment ◽  
Pain Scores ◽  
Postmenstrual Age ◽  
Dosing Strategies

IntroductionAnticipated or actual pain in neonates results in use of paracetamol for prolonged pain relief in many neonatal intensive care units. Clinical trials examining safety of paracetamol exposure in neonates have been of short duration (1–3 days) and hepatic biomarkers and paracetamol metabolism are rarely reported in the same studies.We aim to investigate the safety (hepatic tolerance) and effectiveness of prolonged paracetamol exposure in neonates by measuring hepatic biomarkers, plasma concentrations of paracetamol and its metabolites and pain scores. In addition, we study a possible interaction between ethanol and paracetamol.Methods and analysisA multicentre interventional cohort study.Neonates of any gestational age and up to 44 weeks postmenstrual age, treated with oral or intravenous paracetamol can be included.Alanine aminotransferase (ALT) and bilirubin are measured at baseline or within 24 hours after treatment initiation. P-paracetamol and metabolites are measured at steady state and every 2 days (opportunistically) together with ALT and bilirubin and lastly after discontinuation of treatment. COMFORT neo pain scores are collected longitudinally. COMFORT neo pain scores and population pharmacokinetic analysis of paracetamol samples will be analysed simultaneously using non-linear mixed effects models. One and two compartment models with first-order elimination will be tested for disposition. In addition, plasma ethanol is measured if the patient receives concomitant treatment with intravenous or oral phenobarbital containing ethanol as an excipient.Ethics and disseminationInclusion of patients can be postponed 24 hours after the first paracetamol dose. This is intended to make the inclusion process less stressful for parents. This study uses standard dosing strategies. The potential risks are additional blood samples, which are collected opportunistically to reduce additional heel pricks.Trial registrationnumberEthics Comittee: H-17027244, EudraCT no: 2017-002724-25, BFH-2017–106, 05952.

scholarly journals Population Pharmacokinetic Assessment of Vancomycin Dosing in the Large Pediatric Patient

2019 ◽  
Vol 63 (4) ◽  
Author(s):  
Brady S. Moffett ◽  
Vijay Ivaturi ◽  
Jennifer Morris ◽  
Ayse Akcan Arikan ◽  
Ankhi Dutta
Keyword(s):  
Pediatric Patients ◽  
Population Pharmacokinetic Analysis ◽  
Fat Free Mass ◽  
Pharmacokinetic Analysis ◽  
Population Pharmacokinetic ◽  
Kidney Dysfunction ◽  
Time Curve ◽  
Concentration Time ◽  
Pharmacokinetic Assessment ◽  
Dosing Strategy

ABSTRACT The most appropriate vancomycin dosing strategy in pediatric patients weighing ≥70 kg (weight based versus non-weight based) to achieve an area under the concentration-time curve (AUC) of ≥400 mg·liter/h and a trough concentration of <20 mg/liter is not known. Population pharmacokinetic analysis determined that dosing of vancomycin should be weight based using fat-free mass, with appropriate adjustment for kidney dysfunction.

Population Pharmacokinetic and Concentration-QTc Analysis of Delamanid in Pediatric Participants with Multidrug-Resistant Tuberculosis

2021 ◽  
Author(s):  
Tomohiro Sasaki ◽  
Elin M. Svensson ◽  
Xiaofeng Wang ◽  
Yanlin Wang ◽  
Jeffrey Hafkin ◽  
...  
Keyword(s):  
Plasma Concentrations ◽  
Population Pharmacokinetic Analysis ◽  
Apparent Volume ◽  
Multidrug Resistant ◽  
Volume Of Distribution ◽  
Pharmacokinetic Analysis ◽  
Population Pharmacokinetic ◽  
Resistant Tuberculosis ◽  
Multidrug Resistant Tuberculosis ◽  
Mdr Tb

A population pharmacokinetic analysis of delamanid and its major metabolite DM-6705 was conducted to characterize the pharmacokinetics of delamanid and DM-6705 in pediatric participants with multidrug-resistant tuberculosis (MDR-TB). Data from participants between the ages of 0.67 to 17 years old, enrolled in 2 clinical trials, were utilized for the analysis. The final dataset contained 634 delamanid and 706 DM-6705 valid plasma concentrations from 37 children. A transit model with three compartments best described the absorption of delamanid. Two compartment models for each component with linear elimination were selected to characterize the disposition of delamanid and DM-6705, respectively. The covariates included in the model were body weight on apparent volume of distribution and apparent clearance (for both delamanid and DM-6705); formulation (dispersible vs film coated tablet) on mean absorption time; age, formulation, and dose on bioavailability of delamanid; age on the fraction of delamanid metabolized to DM-6705. Based on the simulations, doses for participants within different age/weight groups that result in delamanid exposure comparable to that in adults following the approved adult dose were calculated. By concentration-QTc (QTcB, QT corrected by Bazett’s' formula) analysis, a significant positive correlation was detected with concentrations of DM-6705. However, the model-predicted upper bounds of the 90% confidence intervals of ΔQTc value were less than 10 ms at the simulated Cmax of DM-6705 following administration of maximum doses simulated. This suggests that the effect on the QT interval following the proposed dosing is unlikely to be clinically meaningful in children with MDR-TB who receive delamanid.

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