The objective of this study was to describe the population pharmacokinetic of meropenem in burn patients and to explore the appropriateness of current dosage regimens. Population pharmacokinetic parameters of meropenem in 59 burn patients were estimated using a mixed effect method (NONMEM, ver. 6.2). The final model chosen was a two-compartment model with first-order elimination […]
2010
Adaptive Bridging Studies in Pharmacokinetics
Background: Bridging study is a concept for extrapolating information gathered from clinical study in an original region, e.g. an adult patient population, to a new region, e.g. a paediatric patient population. Such studies generally include additional pharmacokinetic information to provide knowledge of the time course of exposure in the new region. Since systematic differences are possible […]
Identifiability of random effects parameters in mixed effects models
Identifiability of random effects parameters in mixed effects models In-Sun Nam Knutsson and Leon Aarons School of Pharmacy and Pharmaceutical Sciences The University of Manchester Manchester, U.K. Structural identifiability deals with the ability to uniquely identify parameters given perfect data. A model is said to be globally identifiable if only one set of parameters uniquely […]
Pharmacodynamics of venlafaxine in overdose
Background: Venlafaxine, a serotonin-noradrenalin reuptake inhibitor, appears to be more toxic in overdose than other newer antidepressants. Various studies have shown that there is an increased risk of seizures [1], a potential for cardiac toxicity [2] and a higher rate of fatalities [3] with venlafaxine overdose when compared to other antidepressants. A population pharmacokinetic (PK) analysis […]
Predicting the antimalarial effect of artesunate-mefloquine combination therapy using a mechanistic pharmacokinetic-pharmacodynamic model
Background: Malaria is a mosquito-borne infectious disease, with the most severe form caused by the parasite Plasmodium falciparum. The first-line defence against uncomplicated falciparum malaria is artemisinin-based combination therapy (ACT), involving multiple administrations of two or more antimalarial drugs. ACTs are highly effective worldwide, however, recently decreased efficacy of the ACT artesunate-mefloquine has been reported […]
Optimal designs for warfarin INR monitoring
Background: Warfarin is used to treat and prevent blood clots. It is one of the most difficult drugs to dose accurately, with daily maintenance doses varying by more than tenfold between patients. Evidence from pharmacogenetic studies indicates the importance of CYP2C9 and VKORC1 polymorphisms in predicting warfarin dose variability. However, this information is of limited value […]
A mathematical model for the effect of malaria on arginine catabolism in endothelial cells
Background: Malaria is an infectious disease caused by protozoan parasites from the genus Plasmodium. P. falciparum infects red blood cells (RBCs) which thus adhere to the microvascular endothelium. The accumulation of infected RBCs cause the reduction of oxygen resulting in impaired perfusion and, eventually, organ damage [1]. The characteristics of severe malaria are decreased nitric […]
Evaluation of an optimal design for examining melphalan pharmacokinetics in patients with multiple myeloma
Background: The optimal design of population pharmacokinetics allows parameter estimation with minimum variance and reduced cost by identifying (1) the minimum number of blood samples required from each subject, (2) the optimal blood sampling times and (3) the minimum number of subjects required. Aim: To evaluate the results of an optimal design experiment that was […]
Population Pharmacokinetics of Vancomycin in Premature Malaysian Neonates: Identification of Predictors for Dosing Determination in the First Month of Life
Background: Nothing is known of the pharmacokinetics of vancomycin in premature Malaysian infants during the first month of life. Knowledge of the factors which affect the fate of vancomycin in these infants could lead to improved dosage regimens for this antibiotic. Methods: A one-compartment infusion model with first-order elimination was fitted to serum vancomycin concentration […]
A population PK-PD model of unbound Docetaxel in patients with liver impairment and identification of potential covariates for initial dosage adjustment
Objectives: Docetaxel is a commonly used anti-cancer drug. Due to higher incidence of severe neutropenia in patients with impaired liver function it is rarely given to these patients. A PK model including covariates on clearance (BSA, AAG, LF and ERMBT) have been developed for total and unbound docetaxel in normal and liver impaired patients [1]. […]