Simultaneous modelling of flosequinan and its metabolite.

Design: A randomised, double-blind, prospective, placebo-controlled four-way study of the pharmacokinetics of single oral doses of flosequinan. We do not report the placebo data in this paper. Flosequinan was given at doses of 50, 100 and 150 mg, with a 2-week wash-out between periods.

Generalized nonlinear models for pharmacokinetic data.

Phase I trials to study the pharmacokinetic properties of a new drug generally involve a restricted number of healthy volunteers. Because of the nature of the group involved in such studies, the appropriate distributional assumptions are not always obvious. These model assumptions include the actual distribution but also the ways in which the dispersion of responses is allowed to vary over time and the fact that small concentrations of a substance are not easily detectable and hence are left censored.

Modeling the covariance structure in pharmacokinetic crossover trials.

Pharmacokinetic studies of drug and metabolite concentrations in the blood are usually conducted as crossover trials, especially in phases I and II. A longitudinal series of measurements is collected on each subject within each period. However, much of the dependence among such observations, within and between periods, is generally ignored in analyzing this type of data.

A meta-analysis of nausea and vomiting following maintenance of anaesthesia with propofol or inhalational agents.

A number of prospective randomized comparator studies have suggested that there is a reduction in post-operative nausea and vomiting following maintenance of anaesthesia with propofol compared with inhalational agents. We analysed these studies in more detail by examining the effects of induction agent, choice of inhalation agent, presence/absence of nitrous oxide, age of patient or use of opiate on the incidence of emesis. A search of the Zeneca database MEDLEY was undertaken and prospective randomized comparator studies identified.

Relationship between hypoglycaemic response and plasma concentrations of BTS 67 582 in healthy volunteers.

The relationships between blood glucose, plasma insulin and plasma BTS 67 582 concentrations were studied in a randomised, placebo-controlled, four-way crossover study involving 16 healthy male volunteers aged between 19 and 43 years. Single oral doses of 125, 250 and 500 mg BTS 67 582 were studied. Fasting blood samples were taken pre-dose and half-hourly for 8 h post-dose.