Impact of obesity on the pharmacokinetics of levonorgestrel-based emergency contraception: single and double dosing
| Autor: | Steven W. Blue, Alison Edelman, David W. Erikson, Ganesh Cherala, Jeffrey T. Jensen |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2016 |
| Předmět: |
Adult
endocrine system medicine.medical_specialty Adolescent media_common.quotation_subject Population Cmax Physiology Levonorgestrel Article Body Mass Index 03 medical and health sciences Oregon Young Adult 0302 clinical medicine Pharmacokinetics Internal medicine Follicular phase medicine Humans 030212 general & internal medicine Obesity Prospective Studies Prospective cohort study education Menstrual cycle Menstrual Cycle media_common education.field_of_study 030219 obstetrics & reproductive medicine business.industry Obstetrics and Gynecology Contraceptives Oral Synthetic Endocrinology Reproductive Medicine Case-Control Studies Female business Contraception Postcoital Body mass index medicine.drug |
| Popis: | Objective To determine if differences exist in the pharmacokinetics (PK) of levonorgestrel-based emergency contraception (LNG-EC) in obese and normal body mass index (BMI) users and test whether doubling the dose of LNG-EC in obese women increases total and free (active) LNG serum concentrations. Study design Healthy, reproductive-age women with obese and normal BMIs received 1.5mg LNG orally (ECx1) and then in a subsequent menstrual cycle, the obese group also received 3mg LNG (ECx2). Dosing occurred during the follicular phase. Total and free LNG PK parameters were obtained via serum samples through an indwelling catheter at 0, 0.5, 1, 1.5, 2, and 2.5h. The primary outcome was the difference in total and free LNG concentration maximum (Cmax) between ECx1 and ECx2 in the obese group. Results A total of 10 women enrolled and completed the study (normal BMI=5, median 22.8kg/m 2 , range 20.8–23.7; obese BMI=5, 39.5kg/m 2 , range 35.9–46.7). The total LNG Cmax for obese subjects following ECx1 (5.57±2.48ng/mL) was significantly lower than the level observed in normal BMI women (10.30±2.47, p=.027). Notably, ECx2 increased the Cmax significantly (10.52±2.76, p=.002); approximating the level in normal BMI subjects receiving ECx1. Free LNG Cmax followed a similar pattern. Conclusion Obesity adversely impacts both the total and free Cmax levels of LNG EC and this likely explains its lack of efficacy in obese women. Doubling the dose appears to correct the obesity-related PK changes but additional research is needed to determine if this also improves EC effectiveness in obese women. Implications This study demonstrates that obesity interferes with the pharmacokinetics of LNG EC, and that doubling the dose may be an effective strategy to improve its efficacy in obese women. |
| Databáze: | OpenAIRE |
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