PHARMACOKINETICS OF PROGESTERONE IN POSTMENOPAUSAL WOMEN - 2 - PHARMACOKINETICS FOLLOWING PERCUTANEOUS ADMINISTRATION

Progesterone was administered percutaneously to postmenopausal women i n topical applications on the breast and chest areas in a hydrophilic (gel), lipophilic and an emulsion type base. Venous blood samples were taken 2, 4, 6, 24, 48 and 72 h following administration. The plasma l evels were evaluated by radioimmunoassay. Time of maximum concentratio n (t(max)) was, in all cases, in the neighborhood of 4 h. Mean peak pl asma concentrations were: 1 ng/ml for the lipophilic, 1.24 ng/ml for t he hydrophilic and 2.26 ng/ml for the emulsion type base. The areas un der the curves (AUCs) were practically equivalent for the first two me thods, but higher values were obtained for administration in the emuls ion type base. The elimination was slow, with a half-time varying in t he range of 30-40 h for all three types of base, a value that was much higher than those obtained after administration of progesterone via v aginal suppositories. The AUCs were parallel with the peak plasma conc entrations: almost 2-fold higher for emulsion than for the gel and lip ophilic base. Fit for plasma levels using mono-, bi- and tricompartmen tal models furnished acceptable results only in the case of monocompar tmental model, which raises a number of physiological and physico-chem ical considerations. A 'pseudomonocompartmental' model was constructed to explain this 'anomaly'.