Pharmacokinetics and pharmacodynamics of paclitaxel with carboplatin or gemcitabine, and effects of CYP3A5 and MDR1 polymorphisms in patients with urogenital cancers.

Background: We investigated the pharmacokinetics and pharmacodynamics of paclitaxel with carboplatin or gemcitabine in patients with urogenital cancer to clarify the significance of monitoring of the serum concentration of paclitaxel.

Methods: Paclitaxel was administered at 175 mg/m(2) or 150 mg/m(2) to patients with hormone-refractory prostate cancer (n = 10) or advanced transitional cell carcinoma (n = 6) along with carboplatin or gemcitabine, respectively. The relationships between pharmacokinetic parameters and hematological adverse effects, as well as pharmacological effects, were examined.

Evaluation of Calvert's formula for dosage adjustment of carboplatin in Japanese patients with hormone refractory prostate cancer.

For hormone refractory prostate carcinoma, a combination therapy of paclitaxel and carboplatin is used to expect life extension. We investigated the pharmacokinetics of carboplatin in Japanese prostate cancer patients (n=10, 55-72 years), and evaluated the usefulness of Calvert's formula in the individualized dosing adjustment. They were intravenously administered carboplatin (area under the free plasma concentration versus time curve (AUC)=5 mg.

Altered pharmacokinetics of paclitaxel in experimental hepatic or renal failure.

Purpose: The aim of this study was to investigate the effect of hepatic or renal insufficiency on the pharmacokinetics of paclitaxel in rats.

Methods: Rats were treated with carbon tetrachloride (CCl4; 0.5 ml/kg) to induce hepatic failure or were subjected to 5/6 nephrectomy (5/6 Nx) to induce renal failure.

Evaluation of pharmacokinetic interaction between cyclosporin A and probucol in rats.

Purpose: The purpose of this study was to clarify the mechanism of pharmacokinetic interaction between cyclosporin A and probucol in clinical cases.

Methods: The whole blood concentration of cyclosporin A was measured after oral administration of cyclosporin A with or without probucol in rats. Cyclosporin A was administered as three types of solutions: the contents of the conventional formulation (Sandimmun capsule) diluted with corn oil and the contents of the new microemulsion preconcentrate formulation (Neoral capsule) diluted with saline or corn oil.