2007

Background: Plasma L-arginine is a naturally occurring amino acid that has been found to be reduced in patients with malaria to concentrations below the equilibrium constant (Km) of the cationic amino acid transporter (CAT) needed for intracellular transport and may limit cellular nitric oxide (NO) production. Aim: To develop a pharmacokinetic model for L-arginine in adults with […]

Context: Although population pharmacokinetic and/or pharmacodynamic model evaluation is highly recommended by regulatory authorities, there is no consensus today on the appropriate approach to assess a population model. We have also shown in a recent literature survey [1] that model evaluation was not appropriately performed in most published population pharmacokinetic-pharmacodynamic analyses. Among the different approaches proposed […]

Background: When conducting population pharmacokinetic (PK) analyses, total body weight (WT) is often chosen as a covariate to explain between subject variability in clearance (CL). Given that 99% of the body’s clearance takes place within lean tissues, it has been suggested that WT is unlikely to be suitable for obese subjects and lean body weight (LBW) […]

Objectives: The primary objective of PK/PD modeling in preparation for the First Human Dose study was to estimate a pharmacologically effective dose range in humans based on preclinical data Methods: Data from tumor growth kinetics Xenograft model in mice and from in vivo target inhibition (IVTI) in rats and in mice were incorporated in our PK/PD […]

Background:  Pilot data (n=4 per group) suggests methadone maintenance subjects (MMS) may have increased plasma morphine concentrations compared with controls after the same iv dose (1). Morphine is primarily cleared by hepatic glucuronidation, which is inhibited by methadone in vitro (2).  There has been no previous reported investigation of morphine clearance in the presence of buprenorphine.  Targeting of specific […]

Introduction: Fluconazole (FCZ) is an antifungal drug commonly used in HIV patients. A clinician suspected low concentrations of FCZ in HIV patients, which could be due to saturable input (low bioavailability) or nonlinear disposition of the drug. In contrast, the literature suggests that FCZ concentrations are increased in HIV patients. A study found in the literature […]

Aim: The aim of this study was to i) develop a population pharmacokinetic model for tobramycin in paediatric cystic fibrosis (CF) patients ii) evaluate the influence of covariates, in particular serum creatinine, and iii) test whether tobramycin in CF patients is a candidate for the use in target concentrations intervention (TCI). Methods: Retrospective demographic, dosing and concentration […]

Background: The use of conditional weighted residual (CWRES) and post-hoc ETA (ηph) distribution properties, instead of weighted residual (WRES) distribution properties, as model diagnostic tools when using the first-order conditional (FOCE) algorithm in NONMEM, may give a more accurate picture of if and when a model is miss-specified. Aim: A simulation study was performed to compare these […]

Background: TPV is the first of a new class of non-peptidic PIs, and has potent activity against multiple PI-resistant HIV. To enhance TPV PK, it is combined with low-dose ritonavir. This abstract reports the results of nonlinear mixed effects modeling to characterize the PK of TPV and to elucidate the effects of demographic parameters on the population […]

Bioelectrical impedance analysis measures the impedance to flow of an alternating electrical current passed through biological tissue. Such impedance measurements allow one to estimate fat-free body mass which is an accepted estimate for lean body weight, considered by some to be a better predictor of drug clearance in the obese than, for example, total body […]