Disposition and covalent binding of ibuprofen and its acyl glucuronide in the elderly

Marta Castillo, Yui-wing F Lam, Mary Anne Dooley, Elke Stahl, Philip C. Smith

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Abstract

Ibuprofen is an over-the-counter nonsteroidal anti-inflammatory drug with a low incidence of severe adverse reactions. It is metabolized by oxidation to carboxyibuprofen and hydroxyibuprofen and by conjugation to an acyl glucuronide. In vitro studies have indicated that ibuprofen glucuronide is labile and reactive, forming covalent adducts with proteins. To verify the formation of ibuprofen-protein adducts in vivo, the pharmacokinetics of ibuprofen glucuronide and its covalent binding to plasma proteins were studied in five elderly patients who received long-term administration of oral doses of ibuprofen. Plasma levels of ibuprofen glucuronide were low relative to those of ibuprofen; the ratio of area under the plasma concentration versus time curve for the glucuronide relative to the parent drug was only 4%. Covalent binding of ibuprofen to plasma protein was observed in all patients, correlating well with the area under the plasma concentration versus time curve of ibuprofen glucuronide (r = 0.966). Compared with reports for other nonsteroidal anti-inflammatory drugs that form acyl glucuronides, plasma levels of ibuprofen-protein adduct are low during long-term administration. The observed lower reactivity in vivo is probably attributable to the greater stability of ibuprofen glucuronide relative to other acyl glucuronides.

Original languageEnglish (US)
Pages (from-to)636-644
Number of pages9
JournalClinical Pharmacology and Therapeutics
Volume57
Issue number6
StatePublished - Jun 1995

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Ibuprofen
Glucuronides
Blood Proteins
ibuprofen acyl glucuronide
Anti-Inflammatory Agents
Pharmaceutical Preparations
Proteins
Oral Administration
Pharmacokinetics
Parents

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)

Cite this

Disposition and covalent binding of ibuprofen and its acyl glucuronide in the elderly. / Castillo, Marta; Lam, Yui-wing F; Dooley, Mary Anne; Stahl, Elke; Smith, Philip C.

In: Clinical Pharmacology and Therapeutics, Vol. 57, No. 6, 06.1995, p. 636-644.

Research output: Contribution to journalArticle

Castillo, Marta ; Lam, Yui-wing F ; Dooley, Mary Anne ; Stahl, Elke ; Smith, Philip C. / Disposition and covalent binding of ibuprofen and its acyl glucuronide in the elderly. In: Clinical Pharmacology and Therapeutics. 1995 ; Vol. 57, No. 6. pp. 636-644.
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