Pharmacodynamic evaluation of the benzodiazepine-oral contraceptive interaction.
The sedative, psychomotor, and memory effects of single oral doses of alprazolam (ALP), lorazepam (LOR), temazepam (TMP), and triazolam (TRZ) were evaluated in women taking oral contraceptives (OCs) and a comparable group of control women. Nine women taking OCs and 11 control women took doses of 1 mg ALP and 2 mg LOR and 10 OC users and 10 control women took 30 mg TMP and 0.5 mg TRZ on two occasions separated by 28 days. Minimal psychomotor impairment was noted after TMP. ALP, LOR, and TRZ produced greater performance impairment in the OC users. Correcting the maximum observed performance decrement for plasma concentration did not account for the differences between OC users and controls. After TMP, there was less sedation during the first 2 hours in OC users, who also had higher plasma TMP clearance. There were no differences in sedation between OC users and controls after ALP, LOR, and TRZ; however, there was less than 50% power to detect a 30% difference. Amnestic effects in OC users and controls did not differ after any of the four drugs. The observed patterns of anterograde amnesia were different, with the earliest and most pronounced recognition failure after TRZ (50% at 1.5 hours), while the LOR effect increased to a maximum (30%) 4 hours after dosing. Our data suggest that differences in benzodiazepine pharmacokinetics between OC users and control women do not account for observed differences in psychomotor impairment. Women taking OCs are more sensitive to the psychomotor effects of single oral doses of benzodiazepines.(ABSTRACT TRUNCATED AT 250 WORDS)
Kroboth
P D
PD
Smith
R B
RB
Stoehr
G P
GP
Juhl
R P
RP
D000293:Adolescent; D000328:Adult; D000704:Analysis of Variance; D014151:Anti-Anxiety Agents / Q000378:metabolism / Q000494:pharmacology*; D001569:Benzodiazepines; D003276:Contraceptives, Oral / Q000494:pharmacology*; D004347:Drug Interactions; D005260:Female; D006801:Humans; D006993:Hypnotics and Sedatives / Q000494:pharmacology; D007700:Kinetics; D008568:Memory / Q000187:drug effects; D011597:Psychomotor Performance / Q000187:drug effects
D014151:Anti-Anxiety Agents; D003276:Contraceptives, Oral; D006993:Hypnotics and Sedatives; D001569:Benzodiazepines