Bioavailability study with 2 different levonorgestrel-containing drugs in women

Area of Science:

• Pharmacokinetics
• Drug Bioavailability
• Reproductive Health

Background:

• Levonorgestrel (LNG) is a key progestin in hormonal contraceptives.
• Assessing the bioequivalence of different LNG formulations is crucial for ensuring therapeutic efficacy.
• In vitro dissolution profiles can predict in vivo drug performance.

Purpose of the Study:

• To evaluate the relative bioavailability of a test levonorgestrel product (Mini 30) compared to a reference product (Microval).
• To determine if in vitro dissolution differences influence the rate and extent of drug absorption.
• To assess bioequivalence between Mini 30 and Microval in healthy women.

Main Methods:

• A randomized, single-dose, open crossover study involving 24 healthy women (aged 20-28 years).
• Administration of Mini 30 (0.03 mg levonorgestrel) and Microval.
• Serum levonorgestrel concentrations measured via radioimmunoassay from 0-72 hours post-administration.
• Analysis of pharmacokinetic parameters including AUC0-infinity and Cmax.

Main Results:

• In vitro dissolution: 99.4% of Mini 30 dissolved in 20 min vs. 48.3% of Microval in 45 min.
• In vivo bioequivalence: AUC0-infinity ratio (104.8%) was within acceptance range; Cmax ratio (175.5%) was outside acceptance range.
• Elimination half-lives were similar for both products (approx. 25.4 hours).

Conclusions:

• Mini 30 and Microval demonstrate bioequivalence regarding the extent of levonorgestrel absorption (AUC).
• The rate of levonorgestrel absorption (Cmax) differs significantly between the two products, aligning with in vitro dissolution data.
• While absorption extent is comparable, the faster dissolution of Mini 30 leads to a quicker absorption rate compared to Microval.