Cimetidine inhibits theophylline clearance in patients with chronic obstructive pulmonary disease: a study using stable isotope methodology during multiple oral dose administration.
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.
D000284:Administration, Oral; D000368:Aged; D002247:Carbon Isotopes; D002927:Cimetidine / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology*; D004347:Drug Interactions; D006146:Guanidines / Q000494:pharmacology*; D006801:Humans; D008173:Lung Diseases, Obstructive / Q000097:blood / Q000188:drug therapy*; D008657:Metabolic Clearance Rate; D008875:Middle Aged; D009587:Nitrogen Isotopes; D013806:Theophylline / Q000037:antagonists & inhibitors* / Q000097:blood / Q000378:metabolism; D013997:Time Factors
D002247:Carbon Isotopes; D006146:Guanidines; D009587:Nitrogen Isotopes; D002927:Cimetidine; D013806:Theophylline