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: (a) 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 3mg/kg, lower (65%) after 10mg/kg; (b) 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; (c) 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; (d) 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.