Estradiol pharmacokinetics

No effect of GFJ was observed on 17-beta estradiol (158) or prednisone (160) pharmacokinetics. AUCs were increased for ethinyl-estradiol (159) and methylprednisolone (161). The increases in exposure can be considered weak and seem to be unlikely to be clinically relevant. It has to be mentioned that a decrease in morning cortisol plasma concentrations has been observed after administration of methylprednisolone with GFJ. 

The available case reports in the FDA AERS support the published literature that there are pharmacokinetic interactions between St. John s wort and CYP3A4 and/or p-glycoprotein substrates, such as cyclosporine, levonorgestrel/estradiol and sildenafil, and pharmacodynamic interactions with the SSRIs or MAOI. Subsequent clinical studies including those conducted via a CDER clinical pharmacology research cooperative agreement (14—16) provided mechanistic basis of many of these interactions (refer to Chapter 4). 

Hendrix CW, Jackson KA, Whitmore E, Guidos A, Kretzer R, Liss CM, Shah LP, Khoo K-C, McLane J, Trapnell CB. The effect of isotretinoin on the pharmacokinetics and pharmacodynamics of ethinyl estradiol and norethindrone. Clin Pharmacol Ther 2004 75 464-75. 

Shitara Y, Li AP, Kato Y, et al. Function of uptake transporters for taurocholate and estradiol 17b - D-glucuronide in cryopreserved human hepatocytes. Dmg Metab Pharmacokinet 2003 18 33 41. 

Brody SA, Turkes A, Goldzieher JW. Pharmacokinetics of three bioequivalent norethindrone/mestranol-50 micrograms and three norethindrone/ethinyl estradiol-35 micrograms OC formulations are low-dose pills really lower Contraception 1989 40 269-284. 

Secondary The secondary objective of the study was (i) to assess whether Drug XYZ affects the contraceptive effect of the oral contraceptives containing ethinylestradiol as reflected by changes in serum progesterone and 17- 3-estradiol levels, and (ii) to evaluate the safety, tolerability and pharmacokinetics of repeated once-daily oral doses of Drug XYZ. 

Devissaguet, J. P., Brion, N., Lhote, O., and Deloffre, P. (1999), Pulsed estrogen therapy Pharmacokinetics of intranasal 17 P-estradiol (S21400) in postmenopausal women and... 

Timmer, C. J., and Mulders,T. M. (2000), Pharmacokinetics of etonogestrel and ethinyl-estradiol released from a combined contraceptive vaginal ring, Clin. Pharmacokinet., 39, 233-242. 

Murphy PA,Kem SE, Stanczyk FZ, Westhoff CL. Interaction of St. John s Wort with oral contraceptives effects on the pharmacokinetics of norethindrone and ethinyl estradiol, ovarian activity and breakthrough bleeding. Contraception 2005 71 402-408. 

Estradiol (E2) Not specified Buttocks, abdomen Climara (Berlex Laboratory, Inc.) Pharmacokinetic parameters ATir r T max- buttocks > abdomen. Bioavailability was more variable at abdomen. 

Abrams, L.S. Skee, D.M. Natarajan, J. Wong, F.A. Leese, P.T. Creasy, G.W. Shangold, M.M. Pharmacokinetics of norelgestromin and ethinH estradiol delivered by a contraceptive patch (Ortho Evra /Evra) under conditions of heat humidity, and exercise. J. Clin. Pharmacol. 2001, 41, 1301-1309. 

The polycyclic hydrocarbons in cigarette smoke are potent inducers of certain cytochrome P450 isozymes. There is a marked increase in the 2-hydroxylation of natural estradiol in smokers, but not of ethinylestradiol, suggesting that the two estrogens are metabolized by different P450 enzymes. There is thus probably no pharmacokinetic interaction between smoking and oral... 

Trapnell CB, Donahue SR, Collins JM, Flockhart DA, Thacker D, Abernethy DR. Thalidomide does not alter the pharmacokinetics of ethinyl estradiol and norethin-drone. Clin Pharmacol Ther 1998 64(6) 597-602. 

Rosenfeld WE, Doose DR, Walker SA, Nayak RK. Effect of topiramate on the pharmacokinetics of an oral contraceptive containing norethindrone and ethinyl estradiol in patients with epilepsy. Epilepsia 1997 38(3) 317-23. 

Rahimy MH, Cromie MA, Hopkins NK, Tong DM. Lunelle monthly contraceptive injection (medroxyprogesterone acetate and estradiol cypionate injectable suspension) Effects on body weight and injection sites on pharmacokinetics. Contraception 1999 60 201-208. 

Robinson MR, Baffi J, Yuan P, et al. Safety and pharmacokinetics of intravitreal 2-methoxy-estradiol implants in normal rabbit and pharmacodynamics in a rat model of choroidal neovascularization. Exp Eye Res 2002 74 309-317. 

PHARMACOKINETICS Topiramate is rapidly absorbed after oral administration, exhibits little (10-20%) binding to plasma proteins, and is mainly excreted unchanged in the urine. Its tj is -1 day. Reduced plasma concentrations of estradiol occur with concurrent topiramate, suggesting that low-dose oral contraceptives should be avoided in this setting. 

Pharmacokinetics Most estrogens are well absorbed orally. They tend to be rapidly degraded by the liver during their first pass from the gastrointestinal tract. Metabolites include glucuronide and sulfide conjugates of estradiol, estrone, and estriol. 

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