Pharmacokinetics of theophylline and the H2-antagonist drugs cimetidine and ranitidine.
1984
: This study tested the hypothesis that cimetidine and ranitidine, the new H2-antagonist, may influence the pharmacokinetics of theophylline administered i.v. at two different doses (3.4 and 6.5 mg/kg body wt.). Twenty hospitalized patients with chronic obstructive lung disease (COLD) and peptic ulcer were administered cimetidine or ranitidine orally for 8 days at the routine doses of 2 X 400 mg/day and 2 X 150 mg/day, respectively. Blood samples were collected over a 10-h period before and after H2-antagonist therapy. Cimetidine significantly reduced theophylline clearance, but increased its half-life and the area under the curve (AUC) (p less than 0.001). Ranitidine, on the contrary, did not show any interaction with these pharmacokinetic parameters. Neither of the H2-blocking agents modified the volume of distribution. Furthermore, the delay in theophylline elimination due to cimetidine was more evident at the higher dose of the xanthic drug; this effect induced remarkable changes in plasma theophylline concentrations. Consequently, pharmacokinetic interaction between cimetidine and theophylline may produce serious clinical problems in the management of patients treated with both drugs concurrently, problems which do not arise with ranitidine.
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