Pharmacokinetic interaction between nevirapine and ethinyl estradiol/norethindrone when administered concurrently to HIV-infected women.
OBJECTIVE
To determine the effects of nevirapine (NVP), a nonnucleoside reverse-transcriptase inhibitor of HIV-1 and P450 inducer, on the pharmacokinetics (PK) of ethinyl estradiol (EE)/norethindrone (NET), a widely used oral contraceptive, and to assess the effects of EE/NET on the steady-state PK of NVP.


METHODS
Ten HIV-1-infected women underwent intensive PK sampling after single-dose administration of EE/NET (days 0-1). Oral NVP 200 mg once daily (days 2-15), followed by 200 mg twice daily (days 16-29), was added to background potent antiretroviral therapy. On day 30, intensive PK sampling was performed after concurrent administration of NVP 200 mg and a single dose of EE/NET.


RESULTS
Concomitant administration of NVP at steady state with EE/NET resulted in a significant (29%) median reduction in the area under the plasma concentration time curve (AUC(infinity)) and a significant reduction in mean residence time (MRT) and half-life (t(1/2)) of EE. There was a significant (18%) median reduction in the AUC(infinity) for NET that was not associated with a detectable change in NET C(max), MRT, or t(1/2).


CONCLUSIONS
Oral contraceptives should not be the primary method of birth control in women of child-bearing potential who are treated with NVP.
Mildvan
Donna
D
Division of Infectious Diseases, Beth Israel Medical Center, First Avenue at 16th Street, New York City, NY 10003, U.S.A. mildvan@ix.netcom.com
Yarrish
Robert
R
Marshak
Ann
A
Hutman
Herbert W
HW
McDonough
Marita
M
Lamson
Michael
M
Robinson
Patrick
P
D000328:Adult; D019380:Anti-HIV Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D019540:Area Under Curve; D003277:Contraceptives, Oral, Combined / Q000008:administration & dosage / Q000493:pharmacokinetics*; D004347:Drug Interactions; D004359:Drug Therapy, Combination; D004997:Ethinyl Estradiol / Q000493:pharmacokinetics*; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000378:metabolism; D006801:Humans; D008875:Middle Aged; D019829:Nevirapine / Q000008:administration & dosage / Q000493:pharmacokinetics*; D009640:Norethindrone / Q000493:pharmacokinetics*; D018894:Reverse Transcriptase Inhibitors / Q000008:administration & dosage / Q000493:pharmacokinetics*
D019380:Anti-HIV Agents; D003277:Contraceptives, Oral, Combined; D018894:Reverse Transcriptase Inhibitors; D004997:Ethinyl Estradiol; D019829:Nevirapine; D009640:Norethindrone