Blood oxygen tension-related change of theophylline clearance in experimental hypoxemia

I. Kishimoto, Y. Tanigawara, K. Okumura, R. Hori

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

The effects of arterial blood oxygen tension on the pharmacokinetics of theophylline were investigated using an experimental acute hypoxemia model in rats. Conscious rats were exposed to hypoxic gas composed of 8% O2-92% N2. After blood gas tensions and blood pH were stabilized, rats received 5 mg/kg i.v. theophylline, and urine and blood samples were collected. The steady-state volume of distribution, unbound free fraction and hematocrit were unaffected by hypoxemia. Total body clearance was significantly changed (P<.01) from 0.156 ± 0.020 l/kg/hr in control to 0.0556 ± 0.0067 l/kg/hr in hypoxemic rats due to the reduction of both hepatic and renal clearances. In another constant rate i.v. infusion study, the plateau plasma concentration of theophylline was elevated steeply as soon as animals had inspired hypoxic gas, and the elevated concentrations went down after returning to room air. The present results suggested that the variation of arterial oxygen tension is one possible mechanism for a rapid and large intraindividual variability in theophylline clearance in acutely ill patients with chronic obstructive pulmonary disease.

Original languageEnglish
Pages (from-to)1237-1242
Number of pages6
JournalJournal of Pharmacology and Experimental Therapeutics
Volume248
Issue number3
Publication statusPublished - 1989 Jan 1

    Fingerprint

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmacology

Cite this