The pharmacokinetics of ketoprofen in man during and after repeated oral dosing (50 mg q.i.d.) with Orudis.

Abstract

The pharmacokinetics of ketoprofen were studied in 5 healthy male volunteers after the oral administration of Orudis as a single dose (50 mg) and during, and after a 24-day repeated dosing regimen (50 mg q.i.d.). Levels of ketoprofen in plasma and urine and of conjugated ketoprofen in urine were measured after extraction, by a gas-liquid chromatographic method, which involved the use of a structurally similar internal standard. The minimum level of detection of the method was 40 ng ketoprofen/ml of plasma or 20 ng ketoprofen/ml of urine. The pharmacokinetic parameters obtained following a single oral dose, were comparable with those obtained in previous studies with human subjects from Britain, America and France. Repeated oral administration of a therapeutically effective dose of Orudis (50 mg q.i.d.), resulted in the rapid attainment of a plateau plasma level of ketoprofen, which was maintained throughout the course of dosing. Ketoprofen plasma levels and urinary clearance after the final dose of the 24-day repeated oral dosing regimen, were more variable and generally lower than those found following a single oral dose. However, the early plasma half-lives for the two experiments were similar. It was concluded that in the initial stages of repeated dosing a reduction in ketoprofen absorption, compared to that found after a single oral dose, occurred, and resulted in lower plasma levels of drug.