TY - JOUR
T1 - Increased exposure of norethindrone in HIV + women treated with ritonavir-boosted atazanavir therapy
AU - DuBois, Barent N.
AU - Atrio, Jessica
AU - Stanczyk, Frank Z.
AU - Cherala, Ganesh
N1 - Funding Information:
Acknowledgement of funding: This work was supported by the grant support from the Office Of Women's Health and the National Institutes of Health (Building Interdisciplinary Research Career in Women's Health—2K12HD043488 NICHD), Society of Family Planning and Southern California Clinical and Translational Science Institute (The National Institutes of Health, National Center for Research Resources, and National Center for Advancing Translational Sciences) through Grant UL1TR000130.
Publisher Copyright:
© 2014 Elsevier Inc. All rights reserved.
PY - 2015/1/1
Y1 - 2015/1/1
N2 - Objective: Pharmacokinetics of norethindrone in combination oral contraceptive regimen are well described among HIV + women treated with ritonavir-boosted protease inhibitor therapies; however, such characterization is lacking in women using progestin-only contraception. Our objective is to characterize pharmacokinetics of norethindrone in HIV + women using ritonavir-boosted atazanavir treatment during progestin-only contraceptive regimens. Study design: An open-label, prospective, nonrandomized trial to characterize the pharmacokinetics of norethindrone in HIV + women receiving ritonavir-boosted atazanavir (n= 10; treatment group) and other antiretroviral therapy known to not alter norethindrone levels (n= 17; control group) was conducted. Following informed consent, women were instructed to take a single daily fixed oral dose of 0.35 mg norethindrone and 300 mg/100 mg atazanavir/ritonavir for 22 days. On day 22, serial blood samples were collected by venous catheter at 0, 1, 2, 3, 4, 6, 8, 12, 24, 48 and 72 h. Whole blood was processed to collect serum and stored at - 20°C until later analysis using radioimmunoassay. Pharmacokinetic parameters were estimated using noncompartmental method. Results: In the treatment group, compared to the control group, an increase in area under the curve0-24 (16.69 h∗ng/mL vs. 25.20 h∗ng/mL; p<.05) and maximum serum concentration (2.09 ng/mL vs. 3.19 ng/mL; p<.05), decrease (25%-40%) in apparent volume of distribution and apparent clearance, and unaltered half-life were observed. Conclusion(s): Our findings suggest that progestin-only contraceptives, unlike combination oral contraceptives, benefit from drug-drug interaction and achieve higher levels of exposure. Further studies are needed to establish whether pharmacokinetic interaction leads to favorable clinical outcomes. Implications: Norethindrone-based progestin-only contraceptives, unlike combination oral contraceptives, exhibit greater drug exposure when co-administered with ritonavir-boosted atazanavir regimen and thus may not warrant a category 3 designation by the World Health Organization. Prospective studies are needed to confirm whether pharmacokinetic interaction results in favorable clinical outcomes.
AB - Objective: Pharmacokinetics of norethindrone in combination oral contraceptive regimen are well described among HIV + women treated with ritonavir-boosted protease inhibitor therapies; however, such characterization is lacking in women using progestin-only contraception. Our objective is to characterize pharmacokinetics of norethindrone in HIV + women using ritonavir-boosted atazanavir treatment during progestin-only contraceptive regimens. Study design: An open-label, prospective, nonrandomized trial to characterize the pharmacokinetics of norethindrone in HIV + women receiving ritonavir-boosted atazanavir (n= 10; treatment group) and other antiretroviral therapy known to not alter norethindrone levels (n= 17; control group) was conducted. Following informed consent, women were instructed to take a single daily fixed oral dose of 0.35 mg norethindrone and 300 mg/100 mg atazanavir/ritonavir for 22 days. On day 22, serial blood samples were collected by venous catheter at 0, 1, 2, 3, 4, 6, 8, 12, 24, 48 and 72 h. Whole blood was processed to collect serum and stored at - 20°C until later analysis using radioimmunoassay. Pharmacokinetic parameters were estimated using noncompartmental method. Results: In the treatment group, compared to the control group, an increase in area under the curve0-24 (16.69 h∗ng/mL vs. 25.20 h∗ng/mL; p<.05) and maximum serum concentration (2.09 ng/mL vs. 3.19 ng/mL; p<.05), decrease (25%-40%) in apparent volume of distribution and apparent clearance, and unaltered half-life were observed. Conclusion(s): Our findings suggest that progestin-only contraceptives, unlike combination oral contraceptives, benefit from drug-drug interaction and achieve higher levels of exposure. Further studies are needed to establish whether pharmacokinetic interaction leads to favorable clinical outcomes. Implications: Norethindrone-based progestin-only contraceptives, unlike combination oral contraceptives, exhibit greater drug exposure when co-administered with ritonavir-boosted atazanavir regimen and thus may not warrant a category 3 designation by the World Health Organization. Prospective studies are needed to confirm whether pharmacokinetic interaction results in favorable clinical outcomes.
KW - Norethindrone
KW - Pharmacokinetics
KW - Progestin-only contraception
KW - Ritonavir
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U2 - 10.1016/j.contraception.2014.08.009
DO - 10.1016/j.contraception.2014.08.009
M3 - Article
C2 - 25245190
AN - SCOPUS:84920517749
SN - 0010-7824
VL - 91
SP - 71
EP - 75
JO - Contraception
JF - Contraception
IS - 1
ER -
