Estradiol plasma concentration

Nevirapine induces and is metabolized by CYP3A4 therefore, coadministration of drugs that induce or are metabolized by this isoenzyme may result in interactions. Nevirapine may decrease the effectiveness of ethinyl estradiol-based contraceptives and can lower plasma concentrations of methadone. Nevirapine should not be administered with ketoconazole, rifampin, or rifabutin. 

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. 

Since nevirapine is metabolized by the cytochrome P-450 system and induces 3A4 and 2B6, other drugs that are also metabolized by these isoenzymes will have low plasma levels when given in combination. It also increases the clearance of methadone and results in methadone withdrawal. Nevirapine decreases the plasma concentrations of norethindrone, ethinyl estradiol and protease inhibitors (HIV). 

However, in 12 patients who took letrozole 2.5 mg/day for 6 weeks with and without tamoxifen 20 mg/day plasma concentrations of letrozole were reduced by 38% during combination therapy (39). Tamoxifen did not significantly alter the effect of letrozole in suppressing estradiol, estrone, and estrone sulfate. The authors suggested that sequential therapy might be preferable with these two drugs. 

The effect of continuously administered low-dose 17-beta-estradiol (E2) + norethisterone acetate (NETA) on coagulation and fibrinolytic factors has been studied in 120 menopausal women, using two dosage variations (1 mg of E2 with 0.25 mg or 0.5 mg of NETA) compared with placebo over a year (53). In either dose, the combination significantly lowered plasma concentrations of factor VII, fibrinogen, antithrombin, and plasminogen activator inhibitor-1 (PAI-1) compared with placebo. These changes appear favorable, since they may lead to increased fibrinolytic activity and could reduce the risk of coronary heart disease. However, antithrombin activity was also reduced, which may increase the risk of venous thromboembolism. 

Bergemann N, Mundt C, Parzer P, Jannakos I Nagl I, Salbach B, Klinga K, Runnebaum B, Resch F. Plasma concentrations of estradiol in women suffering from schizophrenia treated with conventional versus atypical antipsychotics. Schizophr Res 2005 73 357-66. 

Hecker, M., W.J. Kim, J.-W. Park, M.B. Murphy, D. Villeneuve, K.K. Coady, P.D. Jones, K.R. Solomon, G. Van Der Kraak, J.A. Carr, E.E. Smith, L. Du Preez, R.J. Kendall, and J.P. Giesy (2005b). Plasma concentrations of estradiol and testosterone, gonadal aromatase activity and ultrastructure of the testis in Xenopus laevis exposed to estradiol or atrazine. Acquat. Toxicol., 72 383-396. 

CICLOSPORIN OESTROGENS Possibly t plasma concentrations of cidosporin Estradiol and immunosuppressants are substrates of CYP3A4 and P-gp. Estradiol is an inhibitor of P-gp Monitor blood cidosporin concentrations. Monitor renal fundion prior to concurrent therapy. Be aware that infections in immunocompromised patients carry a serious threat to life... 

When the transdermal penetration of a drug is inadequate to achieve and maintain a plasma concentration above the minimum therapeutic concentration required to produce the desired effect, a lipophilic prodrug that will be metabolized in the epidermis to the active drug could be used in the development of a controlled-release transdermal delivery system. This approach has been applied to estradiol esters (diacetate and valerate) which are rapidly converted by esterases in the skin tissue to estradiol (Chien et al, 1985). The prodrug serves to increase the transdermal bioavailability of the active drug to which it is converted by metabolism (generally ester hydrolysis) during the percutaneous absorption process. 

There is no experimental evidence that steroid hormone concentrations in serum are different from those in plasma. However, rapid separation of red blood cells in the specimen is important because red blood cells at room temperature can alter plasma concentrations of active steroid hormones red blood cells degrade estradiol to estrone and cortisol to cortisone, and they can adsorb testosterone. 

Boys with 17fi-hydroxysteroid dehydrogenase deficiency fail to form testosterone from androstenedione, androstenediol fi om DHEA, or estradiol from estrone in a normal manner (see Figure 53-4). At puberty, plasma concentrations of testosterone and DHT are low, and plasma androstenedione and estrone are elevated in those individuals. ... 

Because nevirapine induces CYP3A4, this drug may lower plasma concentrations of coadministered CYP3A4 substrates. Methadone withdrawal has been reported in patients receiving nevirapine, presumably as a consequence of enhanced methadone clearance. Plasma ethinyl estradiol and norethindrone concentrations decrease by 20% with nevirapine, and alternative methods of birth control are advised. Nevirapine also can reduce concentrations of some coadministered HIV protease inhibitors. 

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. 

Increased plasma concentrations of norethindrone and ethinyl estradiol... 

TOP decreases the plasma concentrations of the ethinyl estradiol component of oral contraceptives. Women should use an alternative method of birth control or use an oral contraceptive with a higher estrogen content (>35 pg of ethinyl estradiol). 

Granfors MT, Backman JT, Laitila J, Neuvonen PJ. Oral contraceptives containii ethinyl estradiol and gestodene markedfy increase plasma concentrations and effects of tizanidine by inhibiting cytochrome P4501A2. Ctin PhamuKol Ther (2005) 78,400-11. 

In rats provided with suma extract (5 g suma/100 ml water, estimated dose per animal not reported) as the sole source of drinking water for 30 days, increases in plasma concentrations of estradiol-17p and progesterone in female mice, and of testosterone in male mice, were observed (Oshima and Gu 2003). 

Transdermal patches registered at present are patches containing active substances such as buprenorphine, estradiol, fentanyl, glyceryl trinitrate, nicotine, oxybutynine, rivastigmine, rotigotine and scopolamine. These transdermal patches are used in the treatment of a variety of diseases. They release the active substance during a period of 24 up to 72 h, depending on the type of patch used and the active substance. After application of the patch plasma concentration slowly rises until a steady concentration is reached. 

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