Progesterone pharmacokinetics

Besides catalyzing styrene and benzaldehyde, CYP enzymes play an important role in the metabolism of endogenous compounds as well as in pharmacokinetics and toxicokinetics. Joseph [228] developed a biosensor with human CYP3A4 as a novel drugscreening tool. It was constructed by assembling enzyme films on Au electrodes by alternate adsorption of a layer of CYP3A4 on top of a layer of PDDA. The biosensor was applied to detect verapamil, midazolam, quinidine, and progesterone. 

Aebi, S., et al. 1999. A phase II/pharmacokinetic trial of high-dose progesterone in combination with paclitaxel. Cancer Chemother Pharmacol 44 259. 

Miles, R.A., et al. 1994. Pharmacokinetics and endometrial tissue levels of progesterone after administration by intramuscular and vaginal routes A comparative study. Fertil Steril 62 485. 

Mircioiu, C., et al. 1998. Pharmacokinetics of progesterone in postmenopausal women 1. Pharmacokinetics following intravaginal administration. Eur J Drug Metabol Pharmacokin 23 391. 

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. 

Pharmacokinetics Metabolized by liver to glucu-ronide or sulfate conjugates. Most of initial dose is rapidly degraded by first pass metabolism, thus progesterone fails to reach target tissues when administered orally. Synthetic progestins, in contrast, are not susceptible to first pass metabolism and can thus be administered orally. 

There are some limitations as to how progesterone can be administered, because it has relatively low bioavailability when administered orally. The pharmacokinetics for progesterone and its derivatives are listed in Table 46.6. To achieve consistent... 

Telithromycin 800 mg once daily for 10 days had no effect on the pharmacokinetics of ethinylestradiol, but increased the plasma levels of levonorgestrel in 38 healthy women taking a triphasic combined oral contraceptive. None of the women ovulated, as assessed by progesterone levels. ... 

A study in 16 subjects found that pregabalin 200 mg every 8 hours had no effect on the pharmacokinetics of ethinylestradiol or norethisterone taken as a combined oral contraceptive (Orthonovum) and did not reduce the contraceptive effect as measured by progesterone levels. Neither contraceptive steroid had an effect on the pharmacokinetics of pregabalin. No special contraceptive precautions therefore appear to be required during concurrent use. 

A randomised, crossover study in 24 women found that tolterodine 2 mg twice daily on days 1 to 14 of two 28-day contraceptive cycles had no effect on the pharmacokinetics of the steroids in a combined oral contraceptive (ethinylestradioFlevonorgestrel 30/150 micrograms). The pharmacokinetics of the tolterodine were also not significantly altered, and the serum levels of estradiol and progesterone indicated that suppression of ovulation continued during both periods of treatment. No special precautions would therefore seem to be needed if these drugs are used concurrently. 

Intravenous and oral prednisolone was given to 6 post-menopausal women before and after they took progesterone 5 mg for 2 months. The pharmacokinetics of the prednisolone were not significantly altered. ... 

TsunodaSM Harris RZ, MroczkowskiPJ, Hebert MF, Benet LZ. Oral progesterone therapy does not affect the pharmacokinetics of prednisolone and erythromycin in post-menopausal women. CUn Pharmacol Ther (1995) 57,182. 

Many analogs of the endogenous steroids 17p-estradiol, 17P-testosterone, and progesterone (Fig. 1) have been developed by the pharmaceutical industry for therapeutic purposes. Functional groups have been modified or added, by small or larger chemical modifications, to alter the strength and mode of action, to enable oral administration, and to influence other pharmacokinetic properties. 

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