Probenecid alters topotecan (TPT) systemic and renal disposition

W. C. Zamboni, P. J. Houghton, R. K. Johnson, J. L. Hulstein, W. R. Crom, P. J. Cheshire, L. B. Richmond, C. F. Stewart

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

The effect of probenecid on the disposition of TPT lactone (LAC), hydroxy acid (HA), and total (TOT; sum of LAC and HA) was evaluated in mice. Both TPT and HA (1.25 mg/kg i.v.) were administered alone, and with p.o. probenecid 600 (P600) and 1200 mg/kg (P1200) 0.5 hours before and 3 hours after. Serial plasma and urine samples were collected and TPT and TOT measured by HPLC. HA was calculated as the difference between TOT and LAC. AUC (ng-hr/mL) and clearance (CL; L/hr/m2) were estimated from compartmental parameters, and TPT renal CL was calculated. After TPT, P600 reduced TOT renal CL by 50%. Administration TPT TPT TPT HA HA Treatment Alone P600 P1200 Alone P600 LAC AUC 223.1 278.5 319.2 n/a n/a HA AUC n/a n/a n/a 356.0 1297.2 TOT AUC 332.7 511.7 554.8 391.7 1386.9 TPT CL 16.3 13.6 11.8 n/a n/a HA CL n/a n/a n/a 8.8 2.8 These data suggest probenecid primarily inhibits HA renal tubular secretion and increases TPT systemic exposure.

Original languageEnglish (US)
Number of pages1
JournalClinical Pharmacology and Therapeutics
Volume61
Issue number2
StatePublished - Dec 1 1997
Externally publishedYes

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)

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