Menopause: pharmacodynamics and pharmacokinetics.
Effects of menopause on pharmacokinetics and pharmacodynamics remain largely uninvestigated. We described decreased clearance of prednisolone in postmenopausal (POM) vs. premenopausal (PRM) women. Decreased clearance may be related to greater age in POM women, or to hormonal differences between PRM and POM women, independent of age. Estrogen replacement therapy (ERT) did not restore POM pharmacokinetic parameters to PRM values. However, in a single POM woman taking estrogen and progestin, clearance was similar to PRM values, suggesting that estrogen and progestin replacement may restore PRM prednisolone elimination. Lemmens and coworkers reported a significant negative correlation between age and alfentanil clearance in women, but not men, concluding that effects of age on alfentanil clearance were gender dependent. An alternative conclusion based on these same data was proposed by Rubio and Cox, who found that 67.5% of the variation in alfentanil clearance in women was explained when clearance values were divided into groups by menopausal status. Alfentanil clearance may exhibit hormonal dependence, independent of age. These data are consistent with an enzyme system that becomes less active after menopause. Gennari and coworkers examined calcium absorption before and after oophorectomy in women who received ERT or placebo therapy for 6 months after surgery. Placebo women showed significant decreases in vertebral bone density (VBD) and calcium absorption. ERT women maintained presurgical VBD and calcium absorption. The placebo group displayed intestinal resistance to normal 1,25-dihydroxyvitamin D3 stimulation of calcium absorption, whereas ERT preserved normal intestinal responsiveness.
Gustavson
L E
LE
Pharmacokinetics and Biopharmaceutics Department, Abbott Laboratories, Abbott Park, Illinois.
Benet
L Z
LZ
D000328:Adult; D015760:Alfentanil / Q000493:pharmacokinetics; D002117:Calcitriol / Q000494:pharmacology; D002118:Calcium / Q000493:pharmacokinetics; D004967:Estrogens / Q000627:therapeutic use; D005260:Female; D005544:Forecasting; D006801:Humans; D007408:Intestinal Absorption; D008593:Menopause / Q000187:drug effects* / Q000378:metabolism*; D008875:Middle Aged; D010919:Placebos; D011239:Prednisolone / Q000493:pharmacokinetics
D004967:Estrogens; D010919:Placebos; D015760:Alfentanil; D011239:Prednisolone; D002117:Calcitriol; D002118:Calcium