TY - JOUR
T1 - Pharmacokinetic study to compare the absorption and tolerability of two doses of levonorgestrel following single vaginal administration of levonorgestrel in Carraguard® gel
T2 - a new formulation for "dual protection" contraception
AU - Sitruk-Ware, Regine
AU - Brache, Vivian
AU - Maguire, Robin
AU - Croxatto, Horacio
AU - Kumar, Narender
AU - Kumar, Sushma
AU - Montero, Juan Carlos
AU - Salvatierra, Ana Maria
AU - Phillips, David
AU - Faundes, Anibal
N1 - Funding Information:
NICHD Contraceptive Development Center Grant U54 #29990 funded this work.
PY - 2007/6
Y1 - 2007/6
N2 - 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.
AB - 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.
KW - Emergency contraception
KW - Levonorgestrel
KW - Microbicides
KW - SHBG
KW - Vaginal administration
UR - http://www.scopus.com/inward/record.url?scp=34248548508&partnerID=8YFLogxK
U2 - 10.1016/j.contraception.2007.02.003
DO - 10.1016/j.contraception.2007.02.003
M3 - Article
C2 - 17519152
AN - SCOPUS:34248548508
SN - 0010-7824
VL - 75
SP - 454
EP - 460
JO - Contraception
JF - Contraception
IS - 6
ER -