Comparative investigation of the influence of nizatidine, ranitidine, and cimetidine on the steady-state pharmacokinetics of theophylline in COPD patients.
The influence of usual regimens of the H2 blocking drugs, cimetidine, ranitidine, and nizatidine on the steady-state plasma concentrations and pharmacokinetic characteristics of theophylline was studied in seventeen patients with chronic obstructive pulmonary disease (COPD). Patients were dosed to steady-state with an oral, sustained-release formulation of theophylline given in therapeutic doses twice daily for 2 weeks. Over the next 4 weeks, each patient received a week-long regimen of each H2 blocker concomitantly with theophylline, and a week-long regimen of theophylline alone (control). At the end of each of the latter 4 weeks the steady-state pharmacokinetics of theophylline were assessed. Neither ranitidine nor nizatidine treatment altered the steady-state pharmacokinetics of theophylline relative to the control phase (i.e. no H2 blocker treatment). Values for theophylline C(ave), Cssmax, AUC0-12, and CLoral were significantly different during cimetidine treatment compared with all other treatments (ranitidine, nizatidine, and control). Cimetidine increased theophylline Cssmax, AUC0-12 and Cave by approximately 32%, and decreased theophylline oral clearance by approximately 23%. The authors conclude that cimetidine alters the steady-state pharmacokinetics of theophylline in COPD patients, whereas ranitidine and nizatidine are without effect.
Bachmann
K
K
Center for Applied Pharmacology, University of Toledo, Ohio.
Sullivan
T J
TJ
Mauro
L S
LS
Martin
M
M
Jauregui
L
L
Levine
L
L
D000284:Administration, Oral; D000368:Aged; D002927:Cimetidine / Q000494:pharmacology*; D003692:Delayed-Action Preparations; D006801:Humans; D008173:Lung Diseases, Obstructive / Q000188:drug therapy*; D008875:Middle Aged; D016567:Nizatidine / Q000494:pharmacology*; D011899:Ranitidine / Q000494:pharmacology*; D013806:Theophylline / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*
D003692:Delayed-Action Preparations; D002927:Cimetidine; D011899:Ranitidine; D013806:Theophylline; D016567:Nizatidine