The effect of cimetidine on anesthetic metabolism and toxicity.
Because the H2-receptor antagonist cimetidine has been shown to inhibit drug metabolism, the effects of cimetidine on anesthetic metabolism and toxicity were investigated in a rat model. Cimetidine decreased inorganic plasma fluoride production after methoxyflurane administration both in 21% oxygen (P less than 0.001) and in 100% oxygen (P less than 0.001). Phenobarbital produces an increased fluoride formation after methoxyflurane anesthesia, and this fluoride formation is also reduced by cimetidine (P less than 0.005). There was no significant difference between the plasma fluoride levels in rats anesthetized with halothane or enflurane. Although cimetidine inhibited the in vivo defluorination of methoxyflurane, fluoride levels were still within the nephrotoxic range, and cimetidine is not likely to play a role as part of a preanesthetic regimen that would permit the increased clinical use of methoxyflurane. Cimetidine also inhibited the oxidative metabolism of halothane; cimetidine decreased (P less than 0.05) trifluoroacetic acid concentrations after halothane anesthesia in 21% oxygen and in 100% oxygen and decreased (P less than 0.05) bromide concentrations after halothane anesthesia in 100% oxygen. Trifluoroacetic acid levels were less (P less than 0.02) after halothane anesthesia in 14% oxygen as compared with 100% oxygen, indicating a reduction in oxidative metabolism under hypoxic conditions. However, bromide concentrations were maximal after halothane anesthesia in 21% oxygen, and significantly (P less than 0.001) less after halothane anesthesia in 14% and 100% oxygen. Bromide production, therefore, seems to be inhibited by both hypoxia and hyperoxia.(ABSTRACT TRUNCATED AT 250 WORDS)
D000410:Alanine Transaminase / Q000097:blood; D000769:Anesthesia, Inhalation; D000818:Animals; D001711:Biotransformation; D001965:Bromides / Q000097:blood; D002927:Cimetidine / Q000494:pharmacology*; D004347:Drug Interactions; D004737:Enflurane / Q000378:metabolism* / Q000633:toxicity; D005459:Fluorides / Q000097:blood / Q000652:urine; D006221:Halothane / Q000378:metabolism* / Q000633:toxicity; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D008733:Methoxyflurane / Q000378:metabolism* / Q000633:toxicity; D010100:Oxygen / Q000494:pharmacology; D051381:Rats; D011916:Rats, Inbred F344; D011919:Rats, Inbred Strains
D001965:Bromides; D008733:Methoxyflurane; D002927:Cimetidine; D004737:Enflurane; D000410:Alanine Transaminase; D005459:Fluorides; D010100:Oxygen; D006221:Halothane