Levonorgestrel. Clinical Pharmacokinetics

Overview

Journal Clin Pharmacokinet

Specialty Pharmacology

Date 1995 Mar 1

PMID 7758251

Citations 20

Authors

K FOTHERBY

Affiliations

Soon will be listed here.

Abstract

Published values for the serum concentrations and pharmacokinetic parameters of levonorgestrel after administration of various doses of levonorgestrel alone or with ethinylestradiol are reviewed. Most data apply to oral administration of the gestagen, with the smaller amount of data for other modes of administration, e.g. subcutaneous, intravaginal and intra-uterine administration, also included. There is a large variability among the different studies for both serum concentration and pharmacokinetic parameters and not all of this is due to the large interindividual variability demonstrated in all of the studies. The factors responsible for the inter- and intraindividual variability have not been discovered. Sex hormone binding globulin (SHBG) plays an important role in levonorgestrel pharmacokinetics since: (i) levonorgestrel binds strongly to this protein; and (ii) serum SHBG levels are influenced by a large number of different factors including the administration of levonorgestrel and ethinylestradiol. However, not all of the anomalies in the metabolism of levonorgestrel can be ascribed to its interaction with SHBG.

Citing Articles

Suspected Levonorgestrel-Releasing Intrauterine System (LNG-IUS)-Induced Secondary Adrenal Insufficiency: A Case Report.

Joseph A, Corrigan W, Asghar S, Abanilla F Cureus. 2024; 16(8):e66780.

PMID: 39280432 PMC: 11393477. DOI: 10.7759/cureus.66780.

Emerging concepts in male contraception: a narrative review of novel, hormonal and non-hormonal options.

Service C, Puri D, Hsieh T, Patel D Ther Adv Reprod Health. 2023; 17:26334941221138323.

PMID: 36909934 PMC: 9996746. DOI: 10.1177/26334941221138323.

Application of exposure bracketing to streamline the development of contraceptive products.

Brown J, Goodrow T, Hartman D, Hay J, Hershberger K, Hershenson S Contracept X. 2022; 4:100072.

PMID: 35243326 PMC: 8857469. DOI: 10.1016/j.conx.2022.100072.

Atogepant Has No Clinically Relevant Effects on the Pharmacokinetics of an Ethinyl Estradiol/Levonorgestrel Oral Contraceptive in Healthy Female Participants.

Ankrom W, Xu J, Vallee M, Dockendorf M, Armas D, Boinpally R J Clin Pharmacol. 2020; 60(9):1157-1165.

PMID: 32297990 PMC: 7496689. DOI: 10.1002/jcph.1610.

Elbasvir/grazoprevir in women with hepatitis C virus infection taking oral contraceptives or hormone replacement therapy.

Hezode C, Kwo P, Sperl J, Hwang P, Long J, Talwani R Int J Womens Health. 2019; 11:617-628.

PMID: 31819666 PMC: 6875497. DOI: 10.2147/IJWH.S203022.

References

Kuhnz W, Fuhrmeister A . Pharmacokinetics of levonorgestrel and ethinylestradiol in 9 women who received a low-dose oral contraceptive over a treatment period of 3 months and, after a wash-out phase, a single oral administration of the same contraceptive formulation. Contraception. 1992; 46(5):455-69. DOI: 10.1016/0010-7824(92)90149-n. View

Weiner E, Victor A, Johansson E . Plasma levels of d-norgestrel after oral administration. Contraception. 1976; 14(5):563-70. DOI: 10.1016/0010-7824(76)90007-x. View

Nilsson S, Nygren K, Johansson E . d-Norgestrel concentrations in maternal plasma, milk, and child plasma during administration of oral contraceptives to nursing women. Am J Obstet Gynecol. 1977; 129(2):178-84. DOI: 10.1016/0002-9378(77)90741-4. View

Stanczyk F, Lobo R, CHIANG S, WOUTERSZ T . Pharmacokinetic comparison of two triphasic oral contraceptive formulations containing levonorgestrel and ethinylestradiol. Contraception. 1990; 41(1):39-53. DOI: 10.1016/0010-7824(90)90125-f. View

Nilsson C, Johansson E, LUUKKAINEN T . A D-norgestrel-releasing IUD. Contraception. 1976; 13(4):503-14. DOI: 10.1016/s0010-7824(76)80036-4. View

He C, Shi Y, Liao D, Zhu Y, Xu J, Matlin S . Comparative cross-over pharmacokinetic study on two types of postcoital contraceptive tablets containing levonorgestrel. Contraception. 1990; 41(5):557-67. DOI: 10.1016/0010-7824(90)90064-3. View

Abdalla K, Shabaan M, Stanczyk F . Interrelationship of serum levonorgestrel and sex hormone-binding globulin levels following vaginal and oral administration of combined steroid contraceptive tablets. Contraception. 1992; 45(2):111-8. DOI: 10.1016/0010-7824(92)90045-u. View

Alvarez F, Brache V, Faundes A, Johansson E, Odlind V, Nash H . Levonorgestrel plasma levels during continuous administration with different models of subdermal implants. Contraception. 1983; 27(2):123-30. DOI: 10.1016/0010-7824(83)90083-5. View

Shi Y, Zheng S, Zhu Y, He C, Yu P, FOTHERBY K . Pharmacokinetic study of levonorgestrel used as a postcoital agent. Contraception. 1988; 37(4):359-69. DOI: 10.1016/0010-7824(88)90113-8. View

10.

Croxatto H, Diaz S, Pavez M, Cardenas H, Larsson M, Johansson E . Clearance of levonorgestrel from the circulation following removal of NORPLANT subdermal implants. Contraception. 1988; 38(5):509-23. DOI: 10.1016/0010-7824(88)90155-2. View

11.

FOTHERBY K . Interactions of contraceptive steroids with binding proteins and the clinical implications. Ann N Y Acad Sci. 1988; 538:313-20. DOI: 10.1111/j.1749-6632.1988.tb48875.x. View

12.

OLSSON S, Odlind V, Johansson E, Nordstrom M . Plasma levels of levonorgestrel and free levonorgestrel index in women using NORPLANT implants or two covered rods (NORPLANT-2). Contraception. 1987; 35(3):215-28. DOI: 10.1016/0010-7824(87)90024-2. View

13.

Moore D, Roy S, Stanczyk F, Mishell Jr D . Bleeding and serum d-norgestrel, estradiol and progesterone patterns in women using d-norgestrel subdermal polysiloxane capsules for contraception. Contraception. 1978; 17(4):315-28. DOI: 10.1016/0010-7824(78)90078-1. View

14.

FOTHERBY K . Variability of pharmacokinetic parameters for contraceptive steroids. J Steroid Biochem. 1983; 19(1C):817-20. DOI: 10.1016/0022-4731(83)90017-1. View

15.

Victor A, Weiner E, Johansson E . Sex hormone binding globulin: the carrier protein for d-norgestrel. J Clin Endocrinol Metab. 1976; 43(1):244-7. DOI: 10.1210/jcem-43-1-244. View

16.

Noe G, Pavez M, Croxatto H . Changes in serum levels of SHBG, endogenous ligands and levonorgestrel induced by ethinylestradiol in Norplant users. Contraception. 1992; 45(3):187-201. DOI: 10.1016/0010-7824(92)90064-z. View

17.

Song S, Chen J, He M, FOTHERBY K . Effect of some oral contraceptives on serum concentrations of sex hormone binding globulin and ceruloplasmin. Contraception. 1989; 39(4):385-99. DOI: 10.1016/0010-7824(89)90117-0. View

18.

Nair K, Sivakumar B, Prema K, Rao B . Pharmacokinetics of levonorgestrel in Indian women belonging to low socio-economic group. Contraception. 1979; 20(3):303-17. DOI: 10.1016/0010-7824(79)90102-1. View

19.

Weiner E, Johansson E . Plasma levels of d-norgestrel, estradiol and progesterone during treatment with silastic implants containing d-norgestrel. Contraception. 1976; 14(1):81-92. DOI: 10.1016/s0010-7824(76)80011-x. View

20.

Jenkins N, FOTHERBY K . Binding of the contraceptive steroids norgestrel and norethisterone in human plasma. J Steroid Biochem. 1980; 13(5):521-7. DOI: 10.1016/0022-4731(80)90208-3. View