Biowaiver approach for biopharmaceutics classification system class 3 compound metformin hydrochloride using in silico modeling.

The dependency of metformin in vivo disposition on the rate and extent of dissolution was studied. The analysis includes the use of fundamental principles of drug input, permeability, and intestinal transit time within the framework of a compartmental absorption transit model to predict key pharmacokinetic (PK) parameters and then compare the results to clinical data. The simulations show that the maximum plasma concentration (C(max) ) and area under the curve (AUC) are not significantly affected when 100% of drug is released within 2 h of oral dosing, which was confirmed with corresponding human PK data.

Renal insufficiency has no effect on the pharmacokinetics of vicriviroc in a ritonavir-containing regimen.

Background And Objective: Vicriviroc is a small-molecule CCR5 antagonist currently in development for the treatment of HIV in patients on a regimen containing a ritonavir-boosted protease inhibitor. As renal disease and renal dysfunction are prevalent in the HIV-infected population, patients with varying degrees of renal insufficiency may receive vicriviroc, which is metabolized by cytochrome P450 (CYP) 3A4. The present study therefore examined the impact of renal insufficiency on the pharmacokinetics and safety of vicriviroc alone and in the presence of ritonavir, a strong CYP3A4 inhibitor.

Pharmacokinetic/pharmacodynamic modeling of the antiretroviral activity of the CCR5 antagonist Vicriviroc in treatment experienced HIV-infected subjects (ACTG protocol 5211).

Objective: This substudy of AIDS Clinical Trials Group (ACTG) Protocol 5211 explored the relationship between antiretroviral effect and plasma concentrations of vicriviroc, an investigational CCR5 antagonist for HIV infection.

Methods: Eighty-six treatment-experienced subjects failing their current antiretroviral regimens were randomized to add vicriviroc 5, 10, or 15 mg once daily or placebo for 2 weeks. Beyond week 2, subjects were changed to optimized background antiretroviral treatment while continuing vicriviroc or placebo.

Short-term administration of the CCR5 antagonist vicriviroc to patients with HIV and HCV coinfection is safe and tolerable.

Objective: CCR5 antagonists block HIV cell entry through competitive binding to the CCR5 receptor present on the surface of CD4(+) cells. The CCR5 receptor is also present on CD8(+) cells involved in clearing hepatitis C virus (HCV). The goal of the present study was to examine the short-term safety of a CCR5 antagonist, vicriviroc, in patients with HIV/HCV coinfection.

Antiviral activity, pharmacokinetics and safety of vicriviroc, an oral CCR5 antagonist, during 14-day monotherapy in HIV-infected adults.

Objective: To determine antiviral activity, pharmacokinetic properties, and safety of vicriviroc, an orally available CCR5 antagonist, as monotherapy in HIV-infected patients.

Design And Methods: An ascending, multiple dose, placebo-controlled study randomized within treatment group. Forty-eight HIV-infected individuals were enrolled sequentially to dose groups of vicriviroc: 10, 25 and 50 mg twice a day, and were randomly assigned within group to receive vicriviroc or placebo (16 total patients/group) for 14 days.

Desloratadine has no clinically relevant electrocardiographic or pharmacodynamic interactions with ketoconazole.

Objective: This study was performed to assess the electrocardiographic safety and pharmacokinetics of desloratadine in combination with the CYP3A4 inhibitor ketoconazole.

Design: A randomised, placebo-controlled, third-party-blind, 2-way crossover study.

Participants: 24 healthy volunteers (12 men, 12 women; age 19 to 50 years).