Increased exposure of norethindrone in HIV + women treated with ritonavir-boosted atazanavir therapy

Barent N. DuBois, Jessica M. Atrio, Frank Z. Stanczyk, Ganesh Cherala

Research output: Contribution to journalArticle

5 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)71-75
Number of pages5
JournalContraception
Volume91
Issue number1
DOIs
StatePublished - Jan 1 2015

Fingerprint

Norethindrone
Ritonavir
Pharmacokinetics
HIV
Progestins
Oral Contraceptives
Contraceptive Agents
Therapeutics
Control Groups
Protease Inhibitors
Informed Consent
Serum
Contraception
Drug Interactions
Pharmaceutical Preparations
Radioimmunoassay
Half-Life
Atazanavir Sulfate
Catheters
Prospective Studies

Keywords

  • Norethindrone
  • Pharmacokinetics
  • Progestin-only contraception
  • Ritonavir

ASJC Scopus subject areas

  • Reproductive Medicine
  • Obstetrics and Gynecology

Cite this

Increased exposure of norethindrone in HIV + women treated with ritonavir-boosted atazanavir therapy. / DuBois, Barent N.; Atrio, Jessica M.; Stanczyk, Frank Z.; Cherala, Ganesh.

In: Contraception, Vol. 91, No. 1, 01.01.2015, p. 71-75.

Research output: Contribution to journalArticle

DuBois, Barent N. ; Atrio, Jessica M. ; Stanczyk, Frank Z. ; Cherala, Ganesh. / Increased exposure of norethindrone in HIV + women treated with ritonavir-boosted atazanavir therapy. In: Contraception. 2015 ; Vol. 91, No. 1. pp. 71-75.
@article{5b7fe96f1349459a92b253a7ba2482ae,
title = "Increased exposure of norethindrone in HIV + women treated with ritonavir-boosted atazanavir therapy",
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 = "Norethindrone, Pharmacokinetics, Progestin-only contraception, Ritonavir",
author = "DuBois, {Barent N.} and Atrio, {Jessica M.} and Stanczyk, {Frank Z.} and Ganesh Cherala",
year = "2015",
month = "1",
day = "1",
doi = "10.1016/j.contraception.2014.08.009",
language = "English (US)",
volume = "91",
pages = "71--75",
journal = "Contraception",
issn = "0010-7824",
publisher = "Elsevier USA",
number = "1",

}

TY - JOUR

T1 - Increased exposure of norethindrone in HIV + women treated with ritonavir-boosted atazanavir therapy

AU - DuBois, Barent N.

AU - Atrio, Jessica M.

AU - Stanczyk, Frank Z.

AU - Cherala, Ganesh

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

UR - http://www.scopus.com/inward/record.url?scp=84920517749&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84920517749&partnerID=8YFLogxK

U2 - 10.1016/j.contraception.2014.08.009

DO - 10.1016/j.contraception.2014.08.009

M3 - Article

C2 - 25245190

AN - SCOPUS:84920517749

VL - 91

SP - 71

EP - 75

JO - Contraception

JF - Contraception

SN - 0010-7824

IS - 1

ER -