Clinical pharmacokinetics of cidofovir in human immunodeficiency virus- infected patients

K. C. Cundy, B. G. Petty, J. Flaherty, P. E. Fisher, M. A. Polis, M. Wachsman, P. S. Lietman, J. P. Lalezari, M. J.M. Hitchcock, H. S. Jaffe

Research output: Contribution to journalArticlepeer-review

163 Scopus citations


The pharmacokinetics of cidofovir (HPMPC; (S)-1-[3-hydroxy-2- (phosphonylmethoxy)propyl]cytosine) were examined at five dose levels in three phase I/II studies in a total of 42 human immunodeficiency virus- infected patients (with or without asymptomatic cytomegalovirus infection). Levels of cidofovir in serum following intravenous infusion were dose proportional over the dose range of 1.0 to 10.0 mg/kg of body weight and declined biexponentially with an overall mean ± standard deviation terminal half-life of 2.6 ± 1.2 h (n = 25). Approximately 90% of the intravenous dose was recovered unchanged in the urine in 24 h. The overall mean ± standard deviation total clearance of the drug from serum (148 ± 25 ml/h/kg; n = 25) approximated renal clearance (129 ± 42 ml/h/kg; n = 25), which was significantly higher (P < 0.001) than the baseline creatinine clearance in the same patients (83 ± 21 ml/h/kg; n = 12). These data indicate that active tubular secretion played a significant role in the clearance of cidofovir. The steady-state volume of distribution of cidofovir was approximately 500 ml/kg, suggesting that the drug was distributed in total body water. Repeated dosing with cidofovir at 3.0 and 10.0 mg/kg/week did not alter the pharmacokinetics of the drug. Concomitant administration of intravenous cidofovir and oral probenecid to hydrated patients had no significant effect on the pharmacokinetics of cidofovir at a 3.0-mg/kg dose. At higher cidofovir doses, probenecid appeared to block tubular secretion of cidofovir and reduce its renal clearance to a level approaching glomerular filtration.

Original languageEnglish (US)
Pages (from-to)1247-1252
Number of pages6
JournalAntimicrobial agents and chemotherapy
Issue number6
StatePublished - 1995

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)
  • Infectious Diseases


Dive into the research topics of 'Clinical pharmacokinetics of cidofovir in human immunodeficiency virus- infected patients'. Together they form a unique fingerprint.

Cite this