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 was carried out in the rat, mouse and rabbit. The investigation was made using radioactive or unlabeled riapentine and 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 affiity for the adrenals, pancreas and kidneys; concentrations higher tha 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 range between 14-18 h the compound is eliminated mainly via the bile with the 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 h.