Tadalafil population pharmacokinetics in patients with erectile dysfunction.

Objective: The purpose of this study was to characterize pharmacokinetics of tadalafil (Cialis) and potential sources of variability in patients with erectile dysfunction (ED).

Methods: Population models were developed to describe tadalafil pharmacokinetics in 227 patients with mild to severe ED in a phase III trial. Parallel groups of patients received 2, 5, or 10 mg tadalafil or placebo orally, as needed, for 12 weeks.

Effects of gender, age, diabetes mellitus and renal and hepatic impairment on tadalafil pharmacokinetics.

Aims: To evaluate the effects of gender, age, diabetes mellitus, renal and hepatic impairment on tadalafil pharmacokinetics and tolerability.

Methods: Six single-dose (5, 10 or 20 mg orally) clinical pharmacology studies were conducted in the UK, Belgium, Poland and Germany in healthy male and female subjects, elderly subjects and subjects with diabetes mellitus, renal impairment, end-stage renal failure (ESRF) or hepatic impairment. The gender study also incorporated administration of 10 mg tadalafil daily for 10 days.

Model-based drug development: the road to quantitative pharmacology.

High development costs and low success rates in bringing new medicines to the market demand more efficient and effective approaches. Identified by the FDA as a valuable prognostic tool for fulfilling such a demand, model-based drug development is a mathematical and statistical approach that constructs, validates, and utilizes disease models, drug exposure-response models, and pharmacometric models to facilitate drug development. Quantitative pharmacology is a discipline that learns and confirms the key characteristics of new molecular entities in a quantitative manner, with goal of providing explicit, reproducible, and predictive evidence for optimizing drug development plans and enabling critical decision making.

Tadalafil pharmacokinetics in healthy subjects.

Aims: To characterize tadalafil plasma pharmacokinetics in healthy subjects following single and multiple doses.

Methods: Noncompartmental parameters were calculated for healthy subjects receiving a single 2.5-20-mg tadalafil dose in 13 clinical pharmacology studies.

Effect of tadalafil on cytochrome P450 3A4-mediated clearance: studies in vitro and in vivo.

Objectives: Tadalafil was examined in vitro and in vivo for its ability to affect human cytochrome P450 (CYP) 3A-mediated metabolism.

Methods: Reversible and mechanism-based inhibition of CYP3A by tadalafil was examined in human liver microsomes. The ability of tadalafil to influence CYP3A activity was also examined in primary cultures of human hepatocytes.