MedlinePlus a601050 Biological half-life 12–30 hours Molar mass 369.497 g/mol | Legal status US: ℞-only Synonyms ORF-10131 CAS ID 35189-28-7 | |
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AHFS/Drugs.com Micromedex Detailed Consumer Information ATC code G03AA11 (WHO) G03FA13 (WHO) (only combinations with estrogens) | ||
How to pronounce ethinyl estradiol norgestimate ortho tri cyclen memorizing pharmacology
Norgestimate (INN, USAN, BAN) (brand names Ortho-Cyclen, Ortho Tri-Cyclen, Previfem, Sprintec, Prefest, others) is a steroidal progestin of the 19-nortestosterone group that is used in combination with ethinylestradiol as an oral contraceptive and in combination with estradiol in menopausal hormone replacement therapy. It is a prodrug, mainly of norelgestromin, but also of levonorgestrel in small amounts.
Contents
Pharmacology
Norgestimate, unlike other 19-nortestosterone derivatives such as levonorgestrel, shows high selectivity for the progesterone receptor (PR) and low androgenic activity. Moreover, norgestimate and its main active metabolite norelgestromin do not bind to or occupy sex hormone-binding globulin (SHBG). In accordance, clinical trials of norgestimate have observed minimal androgenic side effects.
Androgenic activity
The relative binding affinity of norgestimate and its metabolite norelgestromin for the rat prostatic androgen receptor (AR) are 0.3% and 1.3% of those of dihydrotestosterone (DHT), respectively, whereas the respective values for levonorgestrel and gestodene are 22.0% and 15.4%. Moreover, the ratios of AR to PR binding are 219 for norgestimate and 48 for its metabolite norelgestromin, whereas the ratios of progesterone, levonorgestrel, and gestodene are 93, 11, and 28, respectively.
Estrogens elevate and androgens suppress hepatic production of SHBG and by extension circulating SHBG levels. Clinical studies have found that norgestimate does not appreciably inhibit the increase in SHBG levels produced by ethinylestradiol, and this is in accordance with preclinical research and the notion that norgestimate is minimally androgenic.
Norgestimate and norelgestromin show virtually no affinity for SHBG, unlike levonorgestrel and gestodene (which have 87% and 202% of the relative binding affinity of testosterone for SHBG, respectively) but similarly to progesterone.
Pharmacokinetics
Norgestimate acts as a prodrug to norelgestromin (17β-deacetylnorgestimate or levonorgestrel 3-oxime), the primary active metabolite, and to a lesser extent to levonorgestrel (~22% of an administered dose; deacetylation of norgestimate occurs in the intestines and the liver), as well as to levonorgestrel 17β-acetate in very small quantities.
Chemistry
Norgestimate is also known as norgestrel 17β-acetate 3-oxime (or simply norgestrel acetate oxime) or as 17α-ethynyl-18-methyl-19-nortestosterone 3-oxime 17β-acetate, and is the 3-oxime, 17β-acetate ester of norgestrel.
History
Norgestimate was introduced in 1986.