Pharmacokinetics and metabolism of allopurinol riboside

Theresa A. Shapiro, Joab B.O. Were, Kwame Danso, Donald J. Nelson, Robert E. Desjardins, Charles L. Pamplin

Research output: Contribution to journalArticlepeer-review

15 Scopus citations


There are no safe and effective oral drugs to treat leishmaniasis and Chagas' disease. The safety, pharmacokinetics, and metabolism of single and multiple oral doses of allopurinol riboside, an investigational antiparasitic agent, were evaluated in a randomized, double-blinded, placebo-controlled study in 32 healthy male volunteers, at levels up to 25 mg/kg q.i.d. for 13 doses. No significant toxicity was detected. Allopurinol riboside peaks in plasma 1.6 hours after administration, has an elimination half-life of 3 hours, and steady-state concentrations in the therapeutic range. However, in contrast to preclinical studies in dogs (plasma levels proportional to oral doses up to 200 mg/kg), we found that plasma levels were unexpectedly low and did not rise with increasing dose. Furthermore, allopurinol and oxypurinol (unanticipated metabolites) were detected at levels proportional to the dose of allopurinol riboside. We present a model that includes incomplete absorption, metabolism of residual drug by enteric flora, and absorption of bacterial metabolites to explain these findings in humans.

Original languageEnglish (US)
Pages (from-to)506-514
Number of pages9
JournalClinical pharmacology and therapeutics
Issue number5
StatePublished - May 1991

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)


Dive into the research topics of 'Pharmacokinetics and metabolism of allopurinol riboside'. Together they form a unique fingerprint.

Cite this