Pharmacokinetic consequences of long term coadministration of cimetidine and triazolobenzodiazepines, alprazolam and triazolam, in healthy subjects.
The influence of administration of cimetidine (1 g daily for 2 weeks) on the pharmacokinetics of alprazolam (0.5 mg t.i.d. for 1 week) and triazolam (0.5 mg nightly for 1 week) was investigated in two groups of 8 healthy subjects. The plasma AUC of these triazolobenzodiazepines were significantly increased. Moreover, for triazolam, the C max was increased and the plasma elimination half-life was prolonged; oral clearance of the two triazolobenzodiazepines was markedly reduced. It is suggested that the combined treatment cimetidine-alprazolam requires a reduced daily dosage (one third) of alprazolam or increased dosage intervals (b.i.d. instead of t.i.d.). For triazolam, used as a hypnotic drug, such dosage reduction appears unsuitable if administered on a once-nightly basis.
Pourbaix
S
S
Desager
J P
JP
Hulhoven
R
R
Smith
R B
RB
Harvengt
C
C
D000328:Adult; D000525:Alprazolam; D014151:Anti-Anxiety Agents / Q000008:administration & dosage / Q000378:metabolism*; D001569:Benzodiazepines / Q000008:administration & dosage / Q000378:metabolism*; D002927:Cimetidine / Q000008:administration & dosage / Q000494:pharmacology*; D004347:Drug Interactions; D005260:Female; D006207:Half-Life; D006801:Humans; D007700:Kinetics; D008297:Male; D013997:Time Factors; D014229:Triazolam / Q000008:administration & dosage / Q000378:metabolism*
D014151:Anti-Anxiety Agents; D001569:Benzodiazepines; D014229:Triazolam; D002927:Cimetidine; D000525:Alprazolam