Pooling of clodronate urinary excretion data: a new pharmacokinetic method to study drugs with highly variable gastrointestinal absorption.

Gastrointestinal absorption of bisphosphonates is highly variable from individual to individual (between-subject variation) and from day to day (within-subject variation), a fact that creates problems both in research and in clinical use of these drugs. We conducted a randomized, two-period cross-over pharmacokinetic (phase I) study to assess the relative bioavailability of two different clodronate preparations: an 800 mg tablet and a 400 mg capsule. Urinary excretion of clodronate correlates with gastrointestinal absorption.

Effect of concomitant administration of clodronate and estramustine phosphate on their bioavailability in patients with metastasized prostate cancer.

Estramustine phosphate is generally used as a second-line treatment in patients with advanced prostate cancer. The bone metastases due to the cancer are often treated simultaneously with clodronate in order to relieve the bone pain. Therefore, the interaction of clodronate (800 mg orally four times daily) and estramustine phosphate (280 mg orally twice daily) on their bioavailability was studied in twelve patients with prostate carcinoma and bone metastases.

Effect of food on the bioavailability of oxybutynin from a controlled release tablet.

Objective: The effect of food on the bioavailability of oxybutynin was assessed in a randomised cross-over study in 23 healthy volunteers. A single oral 10 mg dose of a controlled release oxybutynin tablet was administered after a high fat breakfast and to fasting subjects. The AUC, Cmax, tmax, t1/2 and MRT of oxybutynin and its active metabolite N-desethyloxybutynin were determined.

Pharmacokinetics of clodronate in renal failure.

The pharmacokinetic parameters describing the fate of one intravenous clodronate (disodium dichloromethane diphosphonate) dose was studied in 24 normal subjects and in 24 patients with different degrees of renal insufficiency. The aim of the study was to derive data for adjustment of dosage in relation to renal function. Disodium clodronate in serum and urine samples was analyzed by capillary gas chromatography with mass-selective detection.