Pharmacokinetics of rifapentine, a new long lasting rifamycin, in the rat, the mouse and the rabbit.

Abstract

A study on the pharmacokinetics of rifapentine, a new long-lasting rifamycin, has been carried out in the rat, the mouse and the rabbit. The investigation was made using either radioactive or unlabelled rifapentine and both the total 14C and the unchanged compound were assayed. In the rat, the overall evidence obtained was: the oral absorption of rifapentine into central compartment, due to its poor water solubility, appears to be dose-dependent with a satisfactory oral absorption (84%) after a dose of 3 mg/kg, lower (65%) after 10 mg/kg; the antibiotic undergoes rapid liver uptake while it diffuses into the tissue compartment more slowly, with particular affinity for the adrenals, pancreas and kidneys; concentrations higher than in plasma were also measured in the lungs; elimination of rifapentine from the blood and tissue compartments suggests a non linear capacity-limited kinetics where the terminal elimination phase has monoexponential course. Terminal plasma half-life ranged between 14 and 18 hours; the compound is eliminated mainly via the bile with the feces (92% of dose). In mice rifapentine shows a kinetic profile resembling that obtained in rats, whereas in rabbits is metabolized and/or eliminated much more rapidly with a half-life of only 1.8 hours.