The influence of H2 receptor antagonists on the plasma concentrations of midazolam and temazepam.
This study shows that 1 day's treatment with cimetidine or ranitidine causes a raised relative systemic availability of orally administered midazolam (p less than 0.01), but pretreatment with a common emulsion antacid does not alter bioavailability. Temazepam bioavailability after oral administration is unchanged after either H2 receptor antagonist, or after the emulsion antacid. The difference in the systemic availability of the two benzodiazepines following pretreatment with either cimetidine or ranitidine may be explained by inhibition of the mixed function oxidase system in the liver. Drugs with a relatively high liver extraction ratio, such as midazolam, are likely to be affected to a greater extent than those with a low extraction ratio, such as temazepam. The clinical relevance of these findings is yet to be determined.
D000284:Administration, Oral; D000328:Adult; D000863:Antacids / Q000494:pharmacology; D014151:Anti-Anxiety Agents / Q000097:blood*; D001569:Benzodiazepines / Q000008:administration & dosage / Q000097:blood*; D001682:Biological Availability; D002927:Cimetidine / Q000494:pharmacology*; D005260:Female; D006635:Histamine H2 Antagonists / Q000494:pharmacology*; D006801:Humans; D008099:Liver / Q000098:blood supply; D008274:Magnesium / Q000494:pharmacology; D017633:Magnesium Silicates; D008297:Male; D008862:Microsomes, Liver / Q000187:drug effects / Q000201:enzymology; D008874:Midazolam; D008875:Middle Aged; D011899:Ranitidine / Q000494:pharmacology*; D012824:Silicic Acid / Q000494:pharmacology; D013693:Temazepam / Q000008:administration & dosage / Q000097:blood*
D000863:Antacids; D014151:Anti-Anxiety Agents; D006635:Histamine H2 Antagonists; D017633:Magnesium Silicates; D001569:Benzodiazepines; D012824:Silicic Acid; D002927:Cimetidine; D011899:Ranitidine; C001671:magnesium trisilicate; D013693:Temazepam; D008274:Magnesium; D008874:Midazolam