Efflux transport is an important determinant of ethinylestradiol glucuronide and ethinylestradiol sulfate pharmacokinetics.

17α-ethinylestradiol (EE) undergoes extensive conjugation to 17α-ethinylestradiol-3-O-glucuronide (EEG) and 17α-ethinylestradiol-3-O-sulfate (EES). Thus, oral contraceptive drug-drug interaction (DDI) studies usually characterize metabolite pharmacokinetics, with changes typically attributed to modulation of metabolism. EE passively diffuses through plasma membranes, but its conjugates are hydrophilic and require active transport.

Pharmacokinetic interaction between tadalafil and bosentan in healthy male subjects.

Tadalafil, an oral phosphodiesterase 5 (PDE5) inhibitor, is being investigated as a treatment for pulmonary arterial hypertension. Bosentan is an oral endothelin receptor antagonist widely used in the treatment of pulmonary arterial hypertension. Tadalafil is mainly metabolized by cytochrome P450 (CYP) 3A4, and as bosentan induces CYP2C9 and CYP3A4, a pharmacokinetic interaction is possible between these agents.

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.

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.

Pharmacodynamics of oritavancin (LY333328) in a neutropenic-mouse thigh model of Staphylococcus aureus infection.

The pharmacokinetics and pharmacodynamics of oritavancin (LY333328), a glycopeptide antibiotic with concentration-dependent bactericidal activity against gram-positive pathogens, in a neutropenic-mouse thigh model of Staphylococcus aureus infection were studied. Plasma radioequivalent concentrations of oritavancin were determined by using [(14)C]oritavancin at doses ranging from 0.5 to 20 mg/kg of body weight.

The disposition, metabolism, and pharmacokinetics of a selective metabotropic glutamate receptor agonist in rats and dogs.

Compound LY354740 [(+)-2-aminobicyclo[3.1.0]hexane-2,6-dicarboxylic acid], an analog of glutamic acid, is a selective group 2 metabotropic glutamate receptor agonist in clinical development for the treatment of anxiety.