Effect of cytochrome P450 3A4 inducers on the pharmacokinetic, pharmacodynamic and safety profiles of bortezomib in patients with multiple myeloma or non-Hodgkin's lymphoma.

Background And Objective: Bortezomib, an antineoplastic agent with proteasome inhibitory activity, is extensively metabolized by the hepatic microsomal cytochrome P450 (CYP) enzymes CYP3A4 and CYP2C19. Drugs that affect these enzymes may therefore have an impact on the pharmacological profile of bortezomib. This study evaluated the effects of co-administration of a potent CYP3A4 inducer (rifampicin [rifampin]) and a weak CYP3A4 inducer (dexamethasone) on the pharmacokinetic, pharmacodynamic and safety profiles of bortezomib.

Pharmacokinetic model and simulations of dose conversion from immediate- to extended-release tramadol.

Objective: Extended-release tramadol (tramadol ER) is a once-daily formulation of tramadol approved in the United States for moderate to moderately severe chronic pain in adults. This modeling and simulation analysis was conducted to support dosing recommendations for switching patients receiving immediate-release tramadol (tramadol IR) to tramadol ER.

Research Design And Methods: Monte Carlo simulations based on steady-state data from three Phase 1 studies predicted minimum plasma concentration (C(min)), maximum plasma concentration (C(max)), and area under the plasma-concentration-versus-time curve (AUC).

Pharmacokinetics of a contraceptive patch (Evra/Ortho Evra) containing norelgestromin and ethinyloestradiol at four application sites.

Aims: To determine the pharmacokinetic profile of norelgestromin (NGMN) and ethinyloestradiol (EE) following application of the contraceptive patch, Evra/Ortho Evra, at each of four anatomic sites (abdomen, buttock, arm, and torso).

Methods: Thirty-seven healthy, nonpregnant women aged 20-45 years participated in this open-label, four-period crossover study. Subjects were randomized to one of four treatment (site of application) sequences.