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Cimetidine inhibits theophylline clearance in patients with chronic obstructive pulmonary disease: a study using stable isotope methodology during multiple oral dose administration.
Author(s) -
Vestal RE,
Thummel KE,
Musser B,
Mercer GD
Publication year - 1983
Publication title -
british journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.216
H-Index - 146
eISSN - 1365-2125
pISSN - 0306-5251
DOI - 10.1111/j.1365-2125.1983.tb01523.x
Subject(s) - theophylline , cimetidine , volume of distribution , medicine , pharmacokinetics , oral administration , discontinuation , copd , bronchodilator , histamine h2 receptor , endocrinology , pharmacology , asthma , receptor , antagonist
1 The effect of concurrent cimetidine administration on the disposition of theophylline was investigated in eight male patients (56‐78 years) with chronic obstructive pulmonary disease (COPD). 2 The patients, who were taking oral theophylline preparations chronically (384‐1020 mg/day), received a [15N], [13C]‐labelled analogue of theophylline (10 mg i.v.) before and during cimetidine treatment (1200 mg/day p.o.). 3 During cimetidine treatment trough levels of theophylline increased 34% (6.4 +/‐ 0.8 to 8.6 +/‐ 1.0 micrograms/ml, P less than 0.05), half‐life increased 48% (6.5 +/‐ 0.6 to 9.6 +/‐ 0.8 h, P less than 0.001), and total plasma clearance decreased 33% (3.88 +/‐ 0.46 to 2.59 +/‐ 0.33 l/h, P less than 0.001), without a significant change in volume of distribution or protein binding. 4 The effect of cimetidine on plasma levels of theophylline was maximal within 72 h. Levels returned to control values within 48 h after its discontinuation. 5 Although there was no correlation with mean plasma concentrations of cimetidine, the change in clearance of theophylline correlated with initial clearance values (r = 0.72). 6 Cimetidine reduced the plasma clearance of theophylline in patients with COPD to an extent similar to that reported in healthy volunteers.