Pharmacokinetic interaction of nelfinavir and methadone in intravenous drug users.
The effect of nelfinavir 1250 mg twice daily (b.i.d.) on the pharmacokinetics of methadone was determined in 14 HIV-negative methadone users.


METHODS
The methadone dose (20-140 mg/day) was stabilized and fixed for at least 1 month before nelfinavir (1250 mg b.i.d. for 8 days) was added to the regimen. The concentrations of methadone enantiomers were measured before and during nelfinavir treatment, and the concentrations of nelfinavir and its active metabolite, AG1402, were measured during nelfinavir treatment. Adverse events and withdrawal/intoxication symptoms were monitored throughout the study.


RESULTS
Nelfinavir reduced the area under the concentration-time curve of R-methadone, and S-methadone by 43% and 51%, respectively. Nelfinavir and AG1402 concentrations were within the normal range of historical data, and no subject experienced withdrawal symptoms during the study or required dose adjustment during or after the study.


CONCLUSIONS
Although nelfinavir reduced the plasma concentrations of both R- and S-methadone, it seems to have no impact on the maintenance dose of methadone. A routine reduction of methadone dose is not recommended when coadministered with nelfinavir.
Hsyu
Poe-Hirr
PH
Anadys Pharmaceuticals Inc., San Diego, California 92121, USA. phsyu@anadyspharma.com
Lillibridge
Jim
J
Daniels
Elaine
E
Kerr
Bradley M
BM
D000284:Administration, Oral; D000328:Adult; D004347:Drug Interactions; D005260:Female; D017320:HIV Protease Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D006801:Humans; D008297:Male; D008691:Methadone / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000627:therapeutic use; D008875:Middle Aged; D009294:Narcotics / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000627:therapeutic use; D019888:Nelfinavir / Q000008:administration & dosage / Q000494:pharmacology*; D011446:Prospective Studies; D015819:Substance Abuse, Intravenous / Q000534:rehabilitation*
D017320:HIV Protease Inhibitors; D009294:Narcotics; D019888:Nelfinavir; D008691:Methadone