Abstract
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.
Keywords
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Article info
Publication history
Published online: August 29, 2014
Accepted:
August 16,
2014
Received in revised form:
August 4,
2014
Received:
May 30,
2014
Footnotes
☆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.
☆☆Potential financial and other conflicting interests: None.
★Clinical trial registration number: NCT01667978.
Identification
Copyright
© 2014 Elsevier Inc. Published by Elsevier Inc. All rights reserved.
