Effect of tibolone compared with sequential hormone replacement therapy on carbohydrate metabolism in postmenopausal women.

Objective: To investigate the effects of tibolone on carbohydrate metabolism, and to compare these effects with those of a sequential regimen of conjugated equine estrogens and medrogestone.

Methods: This was an open-label, multicentre, comparative study. Seventy-two postmenopausal women were randomized to receive either tibolone 2.

Pharmacokinetics of acetaminophen and ibuprofen when coadministered with telmisartan in healthy volunteers.

Two open-label, two-way, crossover studies were performed to assess any pharmacokinetic interaction of telmisartan with either acetaminophen or ibuprofen. Healthy male adult volunteers (n = 12) received a single oral dose of acetaminophen 1 g alone and with oral telmisartan 120 mg in one study. Oral ibuprofen 400 mg three times daily with and without oral once-daily telmisartan 120 mg was given for 7 days in the other study conducted in 6 males and 6 females.

Sensitivity of repeated interdigital web pinching to detect antinociceptive effects of ibuprofen.

Aims: The aim of the current study was to assess the viability of the interdigital web pinch model as a test for analgesic activity in volunteer-based early phase drug development.

Methods: Pain thresholds and sensitization to a series of four sessions of interdigital web pinching (12 Newtons force) were measured in 26 male volunteers before and 1 and 3 h after oral dosing with ibuprofen (800 mg) or placebo to ibuprofen. Within each time point, the pain thresholds were measured by calculating the average visual analogue scores (VAS) for the first session of pinching (VAS-1).

Optimizing the absorption of valspodar, a P-glycoprotein modulator, Part II: Quantifying its pharmacokinetic variability and refining the bioavailability estimate.

A randomized, sequential, bioreplication study was performed with 24 healthy volunteers to assess the pharmacokinetic variability of oral and intravenous administrations of valspodar, a multidrug resistance modulator for use as a chemotherapy adjunct. Subjects received 200 mg as a 2-hour intravenous infusion and 400 mg orally as microemulsion soft gelatin capsules each given on two separate occasions. Following replicate intravenous administrations, reproducibility in peak concentration and area-under-the-curve was demonstrated by interoccasion equivalence testing.

Pharmacokinetic-pharmacodynamic modelling as a tool to evaluate the clinical relevance of a drug-food interaction for a nisoldipine controlled-release dosage form.

Objective: Nisoldipine, a calcium antagonist of the dihydropyridine class, has been used in the treatment of hypertension and angina pectoris. A new controlled-release dosage form (nisoldipine coat-core, NCC) has been developed to allow once daily dosing. In addition to a formal food interaction study as requested by regulatory authorities for controlled-release dosage forms, a subsequent study was conducted to determine the clinical relevance of the changes in nisoldipine plasma concentration vs time profiles seen in the food effect study.