Selected aspects of the pharmacokinetics and metabolism of ethinyl estrogens and their clinical implications.

Abstract

Careful studies in an adequate sample of subjects show a very marked degree of variability in the pharmacokinetics of ethinyl estradiol--specifically, in parameters such as area under the curve, half-life, and time to peak. This variability is seen in differences between different populations, as well as from one individual to another. These studies also show variability in area under the curve and other parameters in the same person from time to time. Such differences may equal or exceed the differences between low dose (35 micrograms) and high-dose (50 micrograms) formulations. The levels of plasma ethinyl estradiol produced by a 50 micrograms dose of mestranol are similar to those from 35 micrograms of ethinyl estradiol. Thus a high-dose pill may be no higher than a low-dose pill if the nature of the estrogen is not kept in mind. Qualitative differences in the oxidative metabolites of estrogens may be of significance with respect to oncogenic potential.