Pharmacokinetic-pharmacodynamic modelling of the antihistaminic (H1) effect of bilastine.

Objective: To model the pharmacokinetic and pharmacodynamic relationship of bilastine, a new histamine H(1) receptor antagonist, from single- and multiple-dose studies in healthy adult subjects.

Methods: The pharmacokinetic model was developed from different single-dose and multiple-dose studies. In the single-dose studies, a total of 183 subjects received oral doses of bilastine 2.

Pharmacokinetic-pharmacodynamic modeling of the hydroxy lerisetron metabolite L6-OH in rats: an integrated parent-metabolite model.

Purpose: The twofold aim of this study was to characterize in vivo in rats the pharmacokinetics (PK) and pharmacodynamics (PD) of L6-OH, a metabolite of lerisetron with in vitro pharmacological activity, and evaluate the extent to which L6-OH contributes to the overall effect.

Methods: The PK of L6-OH was determined directly postmetabolite i.v.

Age-related changes in pharmacokinetics and pharmacodynamics of lerisetron in the rat: a population pharmacokinetic model.

Background: The importance of studying the effects of age on the pharmacokinetics and pharmacodynamics of lerisetron - a new 5-hydroxytryptamine-3 (serotonin) receptor antagonist - comes from the facts that lerisetron will be administered to patients that are being treated with cytotoxic drugs and that the elderly frequently suffer from neoplastic diseases.

Objective: The present study was designed to explore the effects of age on the pharmacokinetics and pharmacodynamics of lerisetron by using an aged rat model. A mixed-effects population study was carried out in order to analyze the sparse data and to create covariate models which could be used to derive dosage recommendations.

'In vitro' binding of propofol to serum lipoproteins in thyroid dysfunction.

Objective: To determine a regression relationship between the unbound fraction (fu percent) of propofol, a highly lipophilic intravenous anaesthetic agent, and demographic and biochemical variables in a thyroid dysfunction population.

Methods: Serum samples from patients with hypo- (n=33) and hyperthyroidism (n=33) and also from healthy volunteers (control group; n=9) were spiked with propofol to a total (bound + unbound propofol) concentration of 10 microg/ml. The unbound concentration was determined using ultrafiltration followed by high-performance liquid chromatography with fluorimetric detection and the unbound fraction percent (fu) and the binding ratio [bound/free concentration (B/F)] were calculated.

Prediction of unbound propofol concentrations in a diabetic population.

Propofol is a short-acting general intravenous anesthetic characterized by a wide interindividual variability in the response after the same dose. Its binding to serum proteins exceeds 98%, so small changes in protein concentrations can be amplified in the unbound fraction of the drug and hence possibly in the effect. It is then likely that part of the variability in the response could be attributed to differences in protein levels among individuals and particularly among those with pathologies such as diabetes.