Eltrombopag, an oral thrombopoietin receptor agonist, has no impact on the pharmacokinetic profile of probe drugs for cytochrome P450 isoenzymes CYP3A4, CYP1A2, CYP2C9 and CYP2C19 in healthy men: a cocktail analysis.

Purpose: It is likely that the thrombopoietin receptor agonist eltrombopag will be administered concomitantly with other medications in the treatment of thrombocytopenia. Therefore the potential for eltrombopag to interact with cytochrome P450 activity was investigated.

Methods: Twenty-four healthy men received eltrombopag 75 mg/day on days 3-9, midazolam 5 mg (a probe for CYP3A4) on days 1 and 8 and a probe cocktail on days 2 and 9 that included caffeine 100 mg (CYP1A2), flurbiprofen 50 mg (CYP2C9) and omeprazole 20 mg (CYP2C19).

Use of cryopreserved cells for enabling greater flexibility in compound profiling.

Measurement of intracellular calcium release following agonist challenge within cells expressing the relevant membrane protein is a commonly used format to derive structure-activity relationship (SAR) data within a compound profiling assay. The Fluorometric Imaging Plate Reader (FLIPR) has become the gold standard for this purpose. FLIPR traditionally uses cells that are maintained in continuous culture for compound profiling of iterative chemistry campaigns.

Phase 1 clinical study of eltrombopag, an oral, nonpeptide thrombopoietin receptor agonist.

Eltrombopag (SB-497 115) is a first-in-class, oral, small-molecule, nonpeptide agonist of the thrombopoietin receptor (TpoR), being developed as a treatment for thrombocytopenia of various etiologies. In this phase 1 placebo-controlled clinical trial in 73 healthy male subjects, eltrombopag was administered as once-daily oral capsules for 10 days at doses of 5, 10, 25, 30, 50, and 75 mg. The pharmacokinetics of eltrombopag were dose dependent and linear, and eltrombopag increased platelet counts in a dose-dependent manner.

Dextrin sulfate as a vaginal microbicide: randomized, double-blind, placebo-controlled trial including healthy female volunteers and their male partners.

This randomized, placebo-controlled trial assessed the safety and acceptability of vaginally administered 0.125% dextrin sulfate (DS) gel in sexually active women and their male partners. A single 2-mL dose of study gel was self-administered every night over two 14-day periods separated by a 7-day interval, during which menses was expected to occur.

'Chemical condoms' for the prevention of HIV infection: evaluation of novel agents against SHIV(89.6PD) in vitro and in vivo.

Background: Vaginal agents which are antiviral and/or inhibit the entry of HIV into the cell could prevent heterosexual transmission of HIV, and protect women who cannot negotiate condom use.

Methods: Four agents have been investigated for activity in vitro and in vivo against SHIV(89.6PD): two anionic polymers, dextrin-2-sulphate (D2S) and PRO 2000 (P2K), and two virucidal agents; a non-ionic detergent, nonoxynol-9 (N9) and a cyclic peptide ionophore, gramicidin-D (GD).