PHARMACOKINETICS OF TROVAFLOXACIN (CP-99,219), A NEW QUINOLONE, IN RATS, DOGS, AND MONKEYS

The pharmacokinetics of trovafloxacin [CP-99,219; 7-(3-azabicyclo [3.1 .0] hexyl)-naphthyridone] were studied in rats, dogs, and monkeys foll owing oral and intravenous administration. After intravenous dosing, t he systemic clearances of trovafloxacin in rats, dogs, and monkeys wer e 12.5, 11.1, and 7.2 ml/min/kg of body weight, respectively, and the respective volumes of distribution were 0.9, 1.7, and 4.3 liters/kg, w ith corresponding elimination half-lives of 0.7, 1.8, and 7.0 h. After the administration of oral doses of 50, 20, and 20 mg/kg to rats, dog s, and monkeys serum trovafloxacin concentrations reached a maximum at 0.6, 2.3, and 2.3 h, respectively, with respective maximum concentrat ions of trovafloxacin in serum of 11.5, 3.5, and 5.2 mu g/ml; the corr esponding elimination half-lives were 2.2, 2.5, and 7.5 h. The oral bi oavailability of trovafloxacin was 68, 58, and 85% in rats, dogs, and monkeys, respectively. The binding of trovafloxacin to serum proteins was concentration independent, averaging 92, 75, and 66% for rats, dog s, and monkeys, respectively. Trovafloxacin penetrated well into tissu es in dogs. The urinary recoveries of unchanged drug were less than 5% in dogs and monkeys, with or without incubation with alkali or Glusul ase (beta-glucuronidase and sulfatase). In rats, 99.8% of the orally a dministered radioactivity was recovered in feces, while 20.6, 3.4, and 67.1% of the radioactive dose in bile duct-cannulated rats were recov ered in feces, urine, and bile, respectively. These results suggest th at the elimination of trovafloxacin from rats, and possibly from dogs and monkeys, is primarily through biliary excretion.