Teresa Barcellos1, Melissa Natavio2, Frank Z Stanczyk2, Dandan Luo3, William J Jusko4, Nicole M Bender2. 1. Department of Obstetrics and Gynecology, Keck School of Medicine of University of Southern California, Los Angeles, CA 90033, USA. Electronic address: tbarcellos@allcare-med.com. 2. Department of Obstetrics and Gynecology, Keck School of Medicine of University of Southern California, Los Angeles, CA 90033, USA. 3. Department of Biomedical Engineering, University at Buffalo, State University of New York, Buffalo, NY 14260, USA; Department of Pharmaceutical Sciences, University at Buffalo, State University of New York, Buffalo, NY 14214, USA. 4. Department of Pharmaceutical Sciences, University at Buffalo, State University of New York, Buffalo, NY 14214, USA.
Abstract
OBJECTIVE: To assess the pharmacokinetics of combined oral contraceptive (COC) components and prevalence of ovulation in HIV-positive women using ritonavir-containing antiretroviral regimens compared to those using regimens previously found not to interact with COCs or not using any antiretrovirals. STUDY DESIGN: We conducted a prospective cohort pharmacokinetic pilot study comparing the pharmacokinetics of levonorgestrel (LNG) and ethinyl estradiol (EE) in HIV-positive women taking ritonavir-containing antiretroviral regimens to those in women using non-ritonavir-containing regimens or no antiretrovirals. Participants received COCs containing LNG/EE 150/30 mcg for 21 days. Beginning day 21, we collected serial blood samples over 72 h. The primary outcome was area under the curve (AUC) of LNG, with secondary outcomes including other LNG pharmacokinetic measures, EE pharmacokinetics and ovulation as measured by serum progesterone. RESULTS: Pharmacokinetic parameters of LNG showed a trend toward increased exposure in women on ritonavir. LNG AUClast increased by 32.6% (312±60.9 vs. 243±82.6 ng/mL*h, p=.033, n=5) in women taking ritonavir compared to the control group (n=10). The Cmax (9.68±1.81 vs. 7.62±2.29 ng/mL) and Cmin (4.97±1.15 vs. 3.70±1.29 ng/mL) were also higher in the ritonavir arm. After excluding the inconsistent users (n=2), CL of LNG was reduced in the ritonavir arm (p=.032). EE pharmacokinetic profiles were not different between groups. The progesterone concentrations were similar in women of both groups, and none were consistent with ovulation during the treatment cycle. CONCLUSION: Women on ritonavir showed an approximately 30% increase in LNG exposure but no difference in EE exposure. IMPLICATIONS: The current data suggest that ritonavir does not have a clinically significant impact on oral contraceptive pharmacokinetics.
OBJECTIVE: To assess the pharmacokinetics of combined oral contraceptive (COC) components and prevalence of ovulation in HIV-positive women using ritonavir-containing antiretroviral regimens compared to those using regimens previously found not to interact with COCs or not using any antiretrovirals. STUDY DESIGN: We conducted a prospective cohort pharmacokinetic pilot study comparing the pharmacokinetics of levonorgestrel (LNG) and ethinyl estradiol (EE) in HIV-positive women taking ritonavir-containing antiretroviral regimens to those in women using non-ritonavir-containing regimens or no antiretrovirals. Participants received COCs containing LNG/EE 150/30 mcg for 21 days. Beginning day 21, we collected serial blood samples over 72 h. The primary outcome was area under the curve (AUC) of LNG, with secondary outcomes including other LNG pharmacokinetic measures, EE pharmacokinetics and ovulation as measured by serum progesterone. RESULTS: Pharmacokinetic parameters of LNG showed a trend toward increased exposure in women on ritonavir. LNG AUClast increased by 32.6% (312±60.9 vs. 243±82.6 ng/mL*h, p=.033, n=5) in women taking ritonavir compared to the control group (n=10). The Cmax (9.68±1.81 vs. 7.62±2.29 ng/mL) and Cmin (4.97±1.15 vs. 3.70±1.29 ng/mL) were also higher in the ritonavir arm. After excluding the inconsistent users (n=2), CL of LNG was reduced in the ritonavir arm (p=.032). EE pharmacokinetic profiles were not different between groups. The progesterone concentrations were similar in women of both groups, and none were consistent with ovulation during the treatment cycle. CONCLUSION:Women on ritonavir showed an approximately 30% increase in LNG exposure but no difference in EE exposure. IMPLICATIONS: The current data suggest that ritonavir does not have a clinically significant impact on oral contraceptive pharmacokinetics.
Authors: Carolyn L Westhoff; Anupama H Torgal; Elizabeth R Mayeda; Malcolm C Pike; Frank Z Stanczyk Journal: Contraception Date: 2010-02-20 Impact factor: 3.375
Authors: D Ouellet; A Hsu; J Qian; C S Locke; C J Eason; J H Cavanaugh; J M Leonard; G R Granneman Journal: Br J Clin Pharmacol Date: 1998-08 Impact factor: 4.335
Authors: Mary A Vogler; Kristine Patterson; Lori Kamemoto; Jeong-Gun Park; Heather Watts; Francesca Aweeka; Karin L Klingman; Susan E Cohn Journal: J Acquir Immune Defic Syndr Date: 2010-12 Impact factor: 3.731
Authors: Vanitha J Sekar; Eric Lefebvre; Sabrina Spinosa Guzman; Elise Felicione; Martine De Pauw; Tony Vangeneugden; Richard M W Hoetelmans Journal: Antivir Ther Date: 2008
Authors: Gerd Mikus; Kathrin I Foerster; Theresa Terstegen; Cathrin Vogt; André Said; Martin Schulz; Walter E Haefeli Journal: Dtsch Arztebl Int Date: 2022-04-15 Impact factor: 8.251