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Clin Pharmacol Ther. 1984 Jun;35(6):792-7.

Imipramine disposition in users of oral contraceptive steroids.


Ten women on long-term, low-dose estrogen oral contraceptive steroids (OCS) and eight age-matched drug-free female controls received an intravenous infusion of 12.5 mg imipramine. Eleven (six OCS users and five controls) also took a 50-mg oral dose of imipramine on another occasion. After intravenous injection, volume of distribution was much the same in the OCS and control groups and clearance was of the same order (899 and 975 ml/min). Elimination t1/2 was prolonged in OCS users after intravenous doses (17.8 vs 25.5 hr) but did not change after oral doses (18.4 vs 19.1 hr). Imipramine plasma protein binding was of the same order in both groups. Absolute bioavailability increased in OCS users (from 27.1% vs 44.1%), which resulted in a trend toward decreased apparent oral clearance (from 4649 vs 2322 ml/min). Women who used OCS regularly show little change in imipramine kinetics after intravenous dosing. After oral dosing absolute systemic bioavailability increased, resulting in decreased apparent oral clearance in the absence of any change in oral elimination t1/2. Imipramine (with high first-pass hepatic extraction) is nonrestrictively cleared, with drug elimination predominantly a function of hepatic blood flow. These data are consistent with OCS inhibition of hepatic imipramine oxidation with no alteration in hepatic blood flow resulting from chronic OCS use.

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