scholarly journals A population pharmacokinetic model for individualised dosage regimens of vancomycin in Chinese neonates and young infants

Oncotarget ◽  
2017 ◽  
Vol 8 (62) ◽  
pp. 105211-105221 ◽  
Author(s):  
Lin Song ◽  
Cui-Yao He ◽  
Nan-Ge Yin ◽  
Fang Liu ◽  
Yun-Tao Jia ◽  
...  
Keyword(s):  
Population Pharmacokinetic Model ◽  
Pharmacokinetic Model ◽  
Population Pharmacokinetic ◽  
Young Infants ◽  
Dosage Regimens

scholarly journals O11 Characterising the pharmacokinetics of phenobarbitone in neonates to facilitate future individualised dosing

2019 ◽  
Vol 104 (6) ◽  
pp. e5.1-e5 ◽  
Author(s):  
A Williams ◽  
T Donovan ◽  
B Charles ◽  
C Staatz
Keyword(s):  
Oral Bioavailability ◽  
Population Pharmacokinetic Model ◽  
Pharmacokinetic Model ◽  
Volume Of Distribution ◽  
Absolute Bioavailability ◽  
Therapeutic Drug ◽  
Population Pharmacokinetic ◽  
List Type ◽  
Young Infants ◽  
Intravenous And Oral Administration

BackgroundPhenobarbitone is commonly used as a first-line drug in the treatment of neonatal seizures. Previous studies, with small subject numbers, have identified covariates that may influence the pharmacokinetics of phenobarbitone but results have been inconsistent. In particular, oral bioavailability is poorly described with doses reported as being identical for intravenous and oral administration, however, 2 recent studies have reported oral bioavailability of 49% and 59% respectively.1,2MethodsA population pharmacokinetic model was built based on routine therapeutic drug monitoring data from 112 infants at the Royal Brisbane and Women’s Hospital Neonatal Intensive Care Unit. Population modelling was performed using NONMEM 7.3 and PsN 4.7 with assistance from R studio and the packages Xpose and VPC. Body weight with allometric scaling on Clearance (CL) and Volume of Distribution (V) were included a priori in the structural model. Covariates tested included age (post-menstrual, gestational and post-natal), Apgar scores, concomitant phenytoin treatment, infection and method of nutrition.ResultsA one-compartment model provided an adequate fit to the data. Typical clearance increased with patient post-natal age (PNA) and was best modelled using the equation CL = 5.1 *WT0.75 * (PNA/6.25)0.43 (mL/h) were weight is in kg, PNA in days and 6.25 is the median post-natal age. Volume of distribution (V) was best modelled using the equation V = 799 * WT1.0 (mL). Oral bioavailability (F) was 85%. Between-subject variability was 25% and 30% respectively for CL and V.ConclusionThis study describes the largest population pharmacokinetic model of phenobarbitone developed to date with estimates of CL and V similar to previously published models. Estimated F is higher than previously reported but still lower than the implied F of 100% in most recommended dosing regimens. The model could be used to assist with future individualisation of dosing in this cohort.ReferencesMarsot A, et al. Pharmacokinetics and absolute bioavailability of phenobarbital in neonates and young infants, a population pharmacokinetic modelling approach. Fundam Clin Pharmacol 2014;28(4):465–71.Voller S, et al. Model-based clinical dose optimization for phenobarbital in neonates: An illustration of the importance of data sharing and external validation. Eur J Pharm Sci 2017;109s:S90–S97.Disclosure(s)Nothing to disclose

scholarly journals Population Pharmacokinetics of Micafungin in Pediatric Patients and Implications for Antifungal Dosing

2007 ◽  
Vol 51 (10) ◽  
pp. 3714-3719 ◽  
Author(s):  
William W. Hope ◽  
Nita L. Seibel ◽  
Cindy L. Schwartz ◽  
Antonio Arrieta ◽  
Patricia Flynn ◽  
...  
Keyword(s):  
Population Pharmacokinetic Model ◽  
Pharmacokinetic Model ◽  
Drug Exposure ◽  
Pediatric Patients ◽  
Population Pharmacokinetic ◽  
Power Model ◽  
Pharmacokinetic Models ◽  
Dosage Regimens ◽  
Log Likelihood ◽  
Antifungal Efficacy

ABSTRACT The echinocandins potentially have an important role in treatment of infections caused by Candida spp. and Aspergillus spp. in immunocompromised children. However, there are no population pharmacokinetic models of the echinocandins for pediatric patients. The safety and descriptive pharmacokinetics of micafungin in children were recently reported. However, a population pharmacokinetic model in children is needed in order to accurately determine the dosage of micafungin that produces an equivalent magnitude of drug exposure to that observed in adults. In order to explore the effect of weight on micafungin pharmacokinetics, a standard two-compartment pharmacokinetic model, a linear model, and an allometric power model were developed. For all three models, the fit to the data was excellent, with comparable measures of precision and bias. However, the superior log-likelihood value of the allometric power model suggested that it best reflected the data and was therefore chosen for a more detailed analysis of the magnitude and pattern of drug exposure which develop following the administration of micafungin. The allometric power model suggested that clearance in smaller children is higher than that predicted on the basis of weight alone. Consequently, a degree of dosage increase is required in smaller children to ensure comparable levels of drug exposure to those observed in larger children and adults. The allometric power model developed in this study enables identification of pediatric dosage regimens of micafungin which, based upon Monte Carlo simulations, result in equivalent drug exposures to those observed in adults, for which antifungal efficacy has been established.

scholarly journals Population Pharmacokinetic Model for Intravenous ASN100 in Healthy Subjects

2017 ◽  
Vol 4 (suppl_1) ◽  
pp. S529-S529
Author(s):  
Scott A Van Wart ◽  
Christopher Stevens ◽  
Zoltan Magyarics ◽  
Steven A Luperchio ◽  
Paul G Ambrose
Keyword(s):  
Healthy Subjects ◽  
Population Pharmacokinetic Model ◽  
Pharmacokinetic Model ◽  
Population Pharmacokinetic

scholarly journals Pharmacokinetics and Pharmacogenetics of Cyclophosphamide in a Neonate and Infant Childhood Cancer Patient Population

2021 ◽  
Vol 14 (3) ◽  
pp. 272
Author(s):  
Shelby Barnett ◽  
Julie Errington ◽  
Julieann Sludden ◽  
David Jamieson ◽  
Vianney Poinsignon ◽  
...  
Keyword(s):  
Cancer Patient ◽  
Childhood Cancer ◽  
Patient Population ◽  
Population Pharmacokinetic Model ◽  
Pharmacokinetic Model ◽  
Drug Clearance ◽  
Current Data ◽  
Population Pharmacokinetic ◽  
Older Children ◽  
Patient Groups

Infants and young children represent an important but much understudied childhood cancer patient population. The pharmacokinetics and pharmacogenetics of the widely used anticancer prodrug cyclophosphamide were investigated in children <2 years of age. Concentrations of cyclophosphamide and selected metabolites were determined in patients administered cyclophosphamide at doses ranging from 100–1500 mg/m2 (5–75 mg/kg), with various infusion times as determined by the standard treatment regimen that each patient was receiving. Polymorphisms in genes including CYP2B6 and CYP2C19 were investigated. Data generated for cyclophosphamide were analysed using a previously published population pharmacokinetic model. Cyclophosphamide pharmacokinetics was assessed in 111 samples obtained from 25 patients ranging from 4–23 months of age. The average cyclophosphamide clearance for the patients was 46.6 mL/min/m2 (ranging from 9.4–153 mL/min/m2), with marked inter-patient variability observed (CV 41%). No significant differences in cyclophosphamide clearance or exposure (AUC) were observed between patient groups as separated by age or body weight. However, marked differences in drug clearance and metabolism were noted between the current data in children <2 years of age and recently published results from a comparable study conducted by our group in older children, which reported significantly lower cyclophosphamide clearance values and metabolite exposures using the same population pharmacokinetic model for analysis. Whilst this study demonstrates no significant differences in cyclophosphamide clearance in patients <2 years, it highlights large differences in dosing protocols across tumour types. Furthermore, the study suggests marked differences in cyclophosphamide clearance in children less than two years of age as compared to older patients.

scholarly journals Novel Population Pharmacokinetic Model for Linezolid in Critically Ill Patients and Evaluation of the Adequacy of the Current Dosing Recommendation

Pharmaceutics ◽  
2020 ◽  
Vol 12 (1) ◽  
pp. 54 ◽  
Author(s):  
Amaia Soraluce ◽  
Helena Barrasa ◽  
Eduardo Asín-Prieto ◽  
Jose Ángel Sánchez-Izquierdo ◽  
Javier Maynar ◽  
...  
Keyword(s):  
Critically Ill ◽  
Critically Ill Patients ◽  
Population Pharmacokinetic Model ◽  
Pharmacokinetic Model ◽  
Standard Dose ◽  
Compartment Model ◽  
Antimicrobial Treatment ◽  
Population Pharmacokinetic ◽  
Renal Replacement Therapies ◽  
Continuous Renal Replacement Therapies

Antimicrobial treatment in critically ill patients remains challenging. The aim of this study was to develop a population pharmacokinetic model for linezolid in critically ill patients and to evaluate the adequacy of current dosing recommendation (600 mg/12 h). Forty inpatients were included, 23 of whom were subjected to continuous renal replacement therapies (CRRT). Blood and effluent samples were drawn after linezolid administration at defined time points, and linezolid levels were measured. A population pharmacokinetic model was developed, using NONMEM 7.3. The percentage of patients that achieved the pharmacokinetic/pharmacodynamic (PK/PD) targets was calculated (AUC24/MIC > 80 and 100% T>MIC). A two-compartment model best described the pharmacokinetics of linezolid. Elimination was conditioned by the creatinine clearance and by the extra-corporeal clearance if the patient was subjected to CRRT. For most patients, the standard dose of linezolid did not cover infections caused by pathogens with MIC ≥ 2 mg/L. Continuous infusion may be an alternative, especially when renal function is preserved.

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