M. René Bouw

Learn More
1. The objective of this study was to investigate the contribution of the blood-brain barrier (BBB) transport to the delay in antinociceptive effect of morphine-6-glucuronide (M6G), and to study the equilibration of M6G in vivo across the BBB with microdialysis measuring unbound concentrations. 2. On two consecutive days, rats received an exponential(More)
The objective of this study was to investigate the impact of probenecid on the blood-brain barrier (BBB) transport of morphine-3-glucuronide (M3G). Two groups of rats received an exponential infusion of M3G over 4 h to reach a target plasma concentration of 65 microM on two consecutive days. Probenecid was co-administered in the treatment group on day 2.(More)
1. The purpose of the present study was to determine whether intracerebral microdialysis can be used for the assessment of local differences in drug concentrations within the brain. 2. Two transversal microdialysis probes were implanted in parallel into the frontal cortex of male Wistar rats, and used as a local infusion and detection device respectively.(More)
Purpose. To investigate the performance of two alternative retrodialysis recovery methods and to describe the influence of different recoveries on the reliability in estimating unbound extracellular concentrations of morphine. Methods. Unbound concentrations of morphine in striatum and in blood were determined by microdialysis after a 10 min i.v. infusion(More)
The aim of this study was to assess the type I error rate when applying the likelihood ratio (LR) test, for components of the statistical sub-model in NONMEM. Data were simulated from a pharmacokinetic one compartment intravenous bolus model. Two models were fitted to the data, the simulation model and a model containing one additional parameter, and the(More)
Purpose. To quantify the contribution of distributional processes across the blood-brain barrier (BBB) to the delay in antinociceptive effect of morphine in rats. Methods. Unbound morphine concentrations were monitored in venous blood and in brain extracellular fluid (ECF) using microdialysis (MD) and in arterial blood by regular sampling. Retrodialysis by(More)
BACKGROUND AND PURPOSE Biophase equilibration must be considered to gain insight into the mechanisms underlying the pharmacokinetic-pharmacodynamic (PK-PD) correlations of opioids. The objective was to characterise in a quantitative manner the non-linear distribution kinetics of morphine in brain. EXPERIMENTAL APPROACH Male rats received a 10-min infusion(More)
BACKGROUND AND PURPOSE The aim was to investigate the influence of biophase distribution including P-glycoprotein (Pgp) function on the pharmacokinetic-pharmacodynamic correlations of morphine's actions in rat brain. EXPERIMENTAL APPROACH Male rats received a 10-min infusion of morphine as 4 mg kg(-1), combined with a continuous infusion of the Pgp(More)
  • 1