Biomedical subjects

L E Gustavson

Publications and source records attributed to L E Gustavson.

21 records · Page 2Linked to original sources

PubMed1986

Impairment of prednisolone disposition in women taking oral contraceptives or conjugated estrogens.

Companion studies were designed to determine the effects of oral contraceptives and conjugated estrogens on the pharmacokinetics of prednisolone. Twenty-four normal women entered the studies, including six young women taking oral contraceptives and six age-matched control women, and six postmenopausal women receiving conjugated estrogens and six age-matched postmenopausal women. All received 0.53 mg/kg prednisolone phosphate, iv. Significant decreases (P less than 0.05) in the clearance and volume of distribution and significant increases in the half-life were found for both total and unbound prednisolone in the women taking oral contraceptives compared to values in the young control women. A significant decrease in the unbound clearance and increases in the total and unbound half-lives of prednisolone were found in the women receiving conjugated estrogens compared to values in the postmenopausal control women. Total clearance and volume of distribution were unchanged by conjugated estrogen therapy. Administration of prednisolone to women receiving estrogen-containing oral contraceptives or conjugated estrogens results in exposure of these women to increased concentrations of unbound prednisolone for increased periods of time. Increases in the pharmacological and toxic effects of prednisolone might be expected in these women.

Adult↗

PubMed1985

The macromolecular binding of prednisone in plasma of healthy volunteers including pregnant women and oral contraceptive users.

The macromolecular binding of prednisone has been studied in the plasma of eight healthy human volunteers. The subjects included two control males, two control females, two females taking estrogen-containing oral contraceptives, and two females in the third trimester of pregnancy. All volunteers exhibited the expected nonlinear plasma binding of prednisolone with free fraction increasing as the total prednisolone concentration was increased. Both the oral contraceptive and pregnant subjects had increased transcortin binding capacity over the control volunteers as evidenced by their increased binding of prednisolone. Prednisone macromolecular binding, however, was not altered by either changing total prednisone concentration or transcortin binding capacity. The mean prednisone free fraction was 0.250 +/- 0.027 in the eight subjects over the concentration range 0-2500 ng/ml. The addition of prednisolone in up to a 25-fold excess did not alter prednisone's free fraction. Prednisone apparently does not bind to transcortin with the same strong affinity that characterizes prednisolone's binding, and due to albumin's extensive binding capacity, prednisone macromolecular binding is not saturable over the pharmacological drug concentration range.

Adult↗

PubMedDate not supplied

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.

Adult↗