Pharmacokinetic study to compare the absorption and tolerability of two doses of levonorgestrel following single vaginal administration of levonorgestrel in Carraguard® gel: a new formulation for "dual protection" contraception

Regine Sitruk-Ware, Vivian Brache, Robin Maguire, Horacio Croxatto, Narender Kumar, Sushma Kumar, Juan Carlos Montero, Ana Maria Salvatierra, David Phillips, Anibal Faundes

Resultado de la investigación: Article

11 Citas (Scopus)

Resumen

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.

Idioma originalEnglish
Páginas (desde-hasta)454-460
Número de páginas7
PublicaciónContraception
Volumen75
N.º6
DOI
EstadoPublished - 1 jun 2007

Huella dactilar

Intravaginal Administration
Levonorgestrel
Contraception
Pharmacokinetics
Gels
Serum
Contraceptive Agents
Steroids
Foams and Jellies Vaginal Creams
Corpus Luteum
Menstrual Cycle
Sexually Transmitted Diseases
Anti-Infective Agents
Double-Blind Method
Area Under Curve
Progesterone
Mucous Membrane

ASJC Scopus subject areas

  • Medicine(all)
  • Obstetrics and Gynaecology

Citar esto

Sitruk-Ware, Regine ; Brache, Vivian ; Maguire, Robin ; Croxatto, Horacio ; Kumar, Narender ; Kumar, Sushma ; Montero, Juan Carlos ; Salvatierra, Ana Maria ; Phillips, David ; Faundes, Anibal. / Pharmacokinetic study to compare the absorption and tolerability of two doses of levonorgestrel following single vaginal administration of levonorgestrel in Carraguard® gel : a new formulation for "dual protection" contraception. En: Contraception. 2007 ; Vol. 75, N.º 6. pp. 454-460.
@article{01ca744881854989baa1123f55634d7b,
title = "Pharmacokinetic study to compare the absorption and tolerability of two doses of levonorgestrel following single vaginal administration of levonorgestrel in Carraguard{\circledR} gel: a new formulation for {"}dual protection{"} contraception",
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 = "Emergency contraception, Levonorgestrel, Microbicides, SHBG, Vaginal administration",
author = "Regine Sitruk-Ware and Vivian Brache and Robin Maguire and Horacio Croxatto and Narender Kumar and Sushma Kumar and Montero, {Juan Carlos} and Salvatierra, {Ana Maria} and David Phillips and Anibal Faundes",
year = "2007",
month = "6",
day = "1",
doi = "10.1016/j.contraception.2007.02.003",
language = "English",
volume = "75",
pages = "454--460",
journal = "Contraception",
issn = "0010-7824",
publisher = "Elsevier USA",
number = "6",

}

Pharmacokinetic study to compare the absorption and tolerability of two doses of levonorgestrel following single vaginal administration of levonorgestrel in Carraguard® gel : a new formulation for "dual protection" contraception. / Sitruk-Ware, Regine; Brache, Vivian; Maguire, Robin; Croxatto, Horacio; Kumar, Narender; Kumar, Sushma; Montero, Juan Carlos; Salvatierra, Ana Maria; Phillips, David; Faundes, Anibal.

En: Contraception, Vol. 75, N.º 6, 01.06.2007, p. 454-460.

Resultado de la investigación: Article

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

PY - 2007/6/1

Y1 - 2007/6/1

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

VL - 75

SP - 454

EP - 460

JO - Contraception

JF - Contraception

SN - 0010-7824

IS - 6

ER -