Estimating systemic exposure to levonorgestrel from an oral contraceptive

Abstract

Objective The gold standard for measuring oral contraceptive (OC) pharmacokinetics is the 24-hour steady-state area-under-the-curve (AUC). We conducted this study to assess whether limited sampling at steady state or measurements following use of one or two OCs could provide an adequate proxy in epidemiological studies for the progestin 24-hour steady-state AUC of a particular OC. Study Design We conducted a 13-sample, 24-hour pharmacokinetic study on both day 1 and day 21 of the first cycle of a monophasic OC containing 30 μg ethinyl estradiol and 150 μg levonorgestrel (LNG) in 17 normal-weight healthy white women, and a single-dose 9-sample study of the same OC after a one-month washout. We compared the 13-sample steady-state results with several steady-state and single-dose results calculated using parsimonious sampling schemes. Results The 13-sample steady-state 24-hour LNG AUC was highly correlated with the steady-state 24-hour trough value (r = 0.95; 95% CI [0.85, 0.98]) and with the steady-state 6, 8, 12 and 16-hour values (0.92 ≤ r ≤ 0.95). The trough values after one or two doses were moderately correlated with the steady-state 24-hour AUC value (r = 0.70; 95% CI [0.27, 0.90] and 0.77; 95% CI [0.40, 0.92], respectively). Conclusions Single time-point concentrations at steady-state and after administration of one or two OCs gave highly to moderately correlated estimates of steady-state LNG AUC. Using such measures could facilitate prospective pharmaco-epidemiologic studies of the OC and its side effects.

Pharmacokinetics of Oral Levonorgestrel in Women After Roux-en-Y Gastric Bypass Surgery and in BMI-Matched Controls

“…This implies that there is little or no impact of RYGB on the LNG efficacy as a contraceptive. The results of the pharmacokinetic parameters studied were in agreement with previously reported results [27,39,40]. There was a large intra-individual variation in peak serum concentration and AUC, but this was seen in both the RYGB and the control group and is in line with previously reported results [27,41,42].…”

Altered pharmacokinetics of combined oral contraceptives in obesity — multistudy assessment

“…Researchers have been interested in the possibility of using trough or Cmin concentrations of drugs including COCs to monitor exposure and compliance during multiple-dosing. Indeed, reasonable correlations of AUCT and Cmin were found for LNG and EE in small studies of COC products in normal weight women [12,32]. The present study provides data from much larger numbers of subjects than previously with the addition of the disturbances in PK caused by obesity.…”

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

“…In addition, large interindividual variation and intraindividual variation in mean serum concentrations and other PK parameters of LNG after administration of the same dose of LNG have been observed in other studies. 25,26 EE is eliminated through a combination of metabolism via CYP3A, CYP2C, and CYP2E, sulfation, methylation, and glucuronidation. 21,27,28 LNG is rapidly absorbed and does not undergo first-pass metabolism.…”

“…21,27,28 LNG is rapidly absorbed and does not undergo first-pass metabolism. 25,26 The primary metabolic pathways for LNG are oxidation, reduction, and direct sulfation. 21,26,29 Atogepant does not induce or inhibit CYP2D6, CYP3A4, or P-glycoprotein at clinically relevant concentrations, and therefore, drug interactions through CYP450s or UGT1A1 or P-glycoprotein inhibition are unlikely.…”