Clarification of contraceptive drug pharmacokinetics in obesity

Abstract

Related to concerns about the role of obesity in the efficacy of contraceptive drugs, a review of the literature was carried out in regard to the pharmacokinetics of ethinyl estradiol and various progestins given by various routes of administration. Most studies show that obese women exhibit modestly lower plasma concentrations of these drugs (circa 30%) when given the same doses as normal-weight women. While the mechanism is uncertain, precedence in the literature suggests that this is due to body weight-related differences in metabolism rates. Confusing in some of the literature is that a few studies have reported erroneously calculated pharmacokinetic parameters after multiple dosing of oral contraceptives. A demonstration of appropriate pharmacokinetic methodology is provided.

Quantitative Assessment of Levonorgestrel Binding Partner Interplay and Drug‐Drug Interactions Using Physiologically Based Pharmacokinetic Modeling

“…If only free, unbound LNG contributes to the pharmacological action, the relative risks of unintended pregnancy due to DDI would be similar in obese and normal weight women, however, absolute risk may differ. On the other hand, if the “bioavailable hormone hypothesis” (i.e., free + albumin‐LNG concentrations, due to the low affinity binding, the progestin can dissociate from albumin in the tissue capillaries and effectively be available for biological activity) or the megalin‐mediated internalization of SHBG‐LNG complex into target cells, obese women would be under higher risks of contraceptive failure 14,36–38 . Both free and bioavailable hormone hypothesis will be tested within a complementary research project, focusing on exposure‐response relationship for LNG in terms of unintended pregnancy via model‐based meta‐analysis.…”

“…This article is protected by copyright. All rights reserved cells, obese women would be under higher risks of contraceptive failure [14,[36][37][38]. Both, free and bioavailable hormone hypothesis will be tested within a complementary research project, focusing on exposure-response relationship for LNG in terms of unintended pregnancy via model-based meta-analysis.…”

Kontrazeption und Adipositas

“…Studien zeigen hier kontroverse Daten [14]. In einigen Studien wurde gezeigt, dass der pharmakokinetische Prozess sowie die Resorption, der Metabolismus, die renale Exkretion bei erhöhtem Körpergewicht und gesteigerter Fettmasse verändert sind [15][16][17]. Auch der Fettstoffwechsel und der Metabolismus, wie z.…”

Introductory Chapter: Linkages between Pharmacokinetics and Adverse Effects of Drugs

“…It should be said here that atypical or new side effects may occur even with normal doses in certain individuals because of their uniqueness with regard to the receptors, enzymes, or proteins, they may have in abundance or absence thereof as a matter of their genetic makeup or as a result of a subclinical or clinical Pharmacokinetics and Adverse Effects of Drugs -Mechanisms and Risks Factors disease state as well as their lifestyle as already explained. In case of overdose, drug metabolism is altered because enzymes responsible for metabolism become saturated; this leaves the excess drug free to force its way to nonspecific receptors by overcoming both inhibition or competition; consequently, it produces nontypical adverse effects while its clearance is decreased and its half-life is prolonged [27][28][29][30].…”