Abstract
Objective
The study was conducted to assess levonorgestrel (LNG) serum levels achieved after
a single administration of two different doses of Carraguard vaginal gel containing
LNG (CARRA/LNG), designed for use as microbicide and contraceptive for potential dual
protection.
Materials and Methods
This was a randomized double-blind pharmacokinetic study conducted in 12 subjects
enrolled at two centers. Each subject received a single vaginal administration of
CARRA/LNG containing either 0.75 or 1.5 mg LNG per 4 mL of gel on Days 10���12 of
the menstrual cycle. LNG serum levels were measured at 0, 1, 2, 4, 8 and 12 h after
administration and for the following 7 days. LH and progesterone (for a preliminary
evaluation of effect on the ovarian function) as well as SHBG were measured in the
daily samples.
Results
Serum LNG maximum concentrations (Cmax) were 14.1��2.1 and 11.7��2.7 nmol/L and Tmax was 12.0 and 6.0 h for the low and high dose, respectively, with large intersubject
variability within the first 48 h. Mean levels at 96 h were 10% of Cmax. Differences in AUC between both doses were not statistically significant. SHBG levels
decreased approximately 25% by Day 4 after administration. Luteal activity was observed
in 3/6 and 5/6 of the subjects in the low- and high-dose group, respectively.
Conclusion
This study demonstrates that the CARRA/LNG gel can sustain elevated serum levels of
the contraceptive steroid for up to 96 h after a single application. The serum levels
attained with the 0.75-mg formulation are in the range expected to perturb the ovulatory
process as observed in some subjects. The lack of correlation between the administered
dose and serum concentrations of the steroid may be related to a rate-limiting absorption
of LNG from the vaginal mucosa. The results reported here suggest that the CARRA/LNG
formulation has good potential to become a dual-protection method, possibly preventing
conception and sexually transmitted infections.
Keywords
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Article info
Publication history
Published online: April 24, 2007
Accepted:
February 2,
2007
Received in revised form:
January 30,
2007
Received:
July 5,
2006
Identification
Copyright
© 2007 Elsevier Inc. Published by Elsevier Inc. All rights reserved.
