Clinical evaluation of an improved injectable microcapsule contraceptive system

Area of Science:

• Reproductive endocrinology
• Pharmacology
• Biomaterials science

Background:

• Long-acting injectable contraceptives are crucial for family planning.
• Understanding the pharmacokinetics and pharmacodynamics of novel delivery systems is essential for efficacy and safety.
• Poly(DL-lactide-co-glycolide) microcapsules offer potential for sustained drug release.

Purpose of the Study:

• To evaluate the pharmacokinetics and pharmacodynamics of a long-acting injectable norethindrone microcapsule delivery system.
• To assess the contraceptive efficacy and safety profile of this novel formulation.
• To determine the optimal dosage for sustained ovarian suppression.

Main Methods:

• A pharmacokinetic and pharmacodynamic study was conducted in 10 women.
• Two doses of norethindrone (75 or 100 mg) were administered via intramuscular injection using poly(DL-lactide-co-glycolide) microcapsules.
• Ovarian function, ovulation, serum norethindrone levels, endometrial suppression, and adverse effects were monitored.

Main Results:

• All subjects experienced suppressed ovarian function and inhibited ovulation for 3 months.
• Serum norethindrone levels were dose-proportionate, with higher levels observed for the 100 mg dose.
• A biphasic pattern of serum norethindrone levels was noted, with an initial rapid rise and fall, followed by a secondary rise and fall between 10-20 weeks.
• Endometrial suppression occurred for 3 months with minimal adverse effects, primarily spotting and irregular cycles.
• No significant impact on serum lipids was observed.

Conclusions:

• The long-acting injectable norethindrone microcapsule effectively suppresses ovulation and provides contraception for at least 3 months.
• The poly(DL-lactide-co-glycolide) delivery system exhibits predictable pharmacokinetics and a favorable safety profile.
• This formulation represents a promising option for long-term reversible contraception.