Abstract
The pharmacokinetics of trovafloxacin [CP-99,219; 7-(3-azabicyclo[3.1.0]hexyl)-naphthyridone] were studied in rats, dogs, and monkeys following oral and intravenous administration. After intravenous dosing, the systemic clearances of trovafloxacin in rats, dogs, and monkeys were 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, with 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, dogs, and monkeys serum trovafloxacin concentrations reached a maximum at 0.6, 2.3, and 2.3 h, respectively, with respective maximum concentrations of trovafloxacin in serum of 11.5, 3.5, and 5.2 micrograms/ml; the corresponding elimination half-lives were 2.2, 2.5, and 7.5 h. The oral bioavailability 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, dogs, and monkeys, respectively. Trovafloxacin penetrated well into tissues in dogs. The urinary recoveries of unchanged drug were less than 5% in dogs and monkeys, with or without incubation with alkali or Glusulase (beta-glucuronidase and sulfatase). In rats, 99.8% of the orally administered radioactivity was recovered in feces, while 20.6, 3.4, and 67.1% of the radioactive dose in bile duct-cannulated rats were recovered in feces, urine, and bile, respectively. These results suggest that the elimination of trovafloxacin from rats, and possibly from dogs and monkeys, is primarily through biliary excretion.
Full Text
The Full Text of this article is available as a PDF (190.9 KB).
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Boudinot F. D., Jusko W. J. Fluid shifts and other factors affecting plasma protein binding of prednisolone by equilibrium dialysis. J Pharm Sci. 1984 Jun;73(6):774–780. doi: 10.1002/jps.2600730617. [DOI] [PubMed] [Google Scholar]
- Eliopoulos G. M., Klimm K., Eliopoulos C. T., Ferraro M. J., Moellering R. C., Jr In vitro activity of CP-99,219, a new fluoroquinolone, against clinical isolates of gram-positive bacteria. Antimicrob Agents Chemother. 1993 Feb;37(2):366–370. doi: 10.1128/aac.37.2.366. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Faed E. M. Properties of acyl glucuronides: implications for studies of the pharmacokinetics and metabolism of acidic drugs. Drug Metab Rev. 1984;15(5-6):1213–1249. doi: 10.3109/03602538409033562. [DOI] [PubMed] [Google Scholar]
- Fitton A. The quinolones. An overview of their pharmacology. Clin Pharmacokinet. 1992;22 (Suppl 1):1–11. doi: 10.2165/00003088-199200221-00003. [DOI] [PubMed] [Google Scholar]
- Gooding B. B., Jones R. N. In vitro antimicrobial activity of CP-99,219, a novel azabicyclo-naphthyridone. Antimicrob Agents Chemother. 1993 Feb;37(2):349–353. doi: 10.1128/aac.37.2.349. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Gootz T. D., Brighty K. E., Anderson M. R., Schmieder B. J., Haskell S. L., Sutcliffe J. A., Castaldi M. J., McGuirk P. R. In vitro activity of CP-99,219, a novel 7-(3-azabicyclo[3.1.0]hexyl) naphthyridone antimicrobial. Diagn Microbiol Infect Dis. 1994 Aug;19(4):235–243. doi: 10.1016/0732-8893(94)90037-x. [DOI] [PubMed] [Google Scholar]
- Neu H. C., Chin N. X. In vitro activity of the new fluoroquinolone CP-99,219. Antimicrob Agents Chemother. 1994 Nov;38(11):2615–2622. doi: 10.1128/aac.38.11.2615. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Sinclair K. A., Caldwell J. The formation of beta-glucuronidase resistant glucuronides by the intramolecular rearrangement of glucuronic acid conjugates at mild alkaline pH. Biochem Pharmacol. 1982 Mar 15;31(6):953–957. doi: 10.1016/0006-2952(82)90326-4. [DOI] [PubMed] [Google Scholar]
- Teng R., Harris S. C., Nix D. E., Schentag J. J., Foulds G., Liston T. E. Pharmacokinetics and safety of trovafloxacin (CP-99,219), a new quinolone antibiotic, following administration of single oral doses to healthy male volunteers. J Antimicrob Chemother. 1995 Aug;36(2):385–394. doi: 10.1093/jac/36.2.385. [DOI] [PubMed] [Google Scholar]