Ph. Hsyu et al., Pharmacokinetic interactions between nelfinavir and 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors atorvastatin and simvastatin, ANTIM AG CH, 45(12), 2001, pp. 3445-3450
3-Hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors are ef
fective agents in lowering cholesterol and triglycerides and are being used
by human immunodeficiency virus-positive patients to treat the lipid eleva
tion that may be associated with antiretroviral therapy. Many HMG-CoA reduc
tase inhibitors and protease inhibitors are metabolized by the same cytochr
ome P450 enzyme 3A4 (CYP3A4). In addition, many protease inhibitors are pot
ent inhibitors of CYP3A4. Therefore, coadministration of these two classes
of drugs may cause significant drug interactions. This open-label, multiple
-dose study was performed to determine the interactions between nelfinavir,
a protease inhibitor, and two HMG-CoA reductase inhibitors, atorvastatin a
nd simvastatin, in healthy volunteers. Thirty-two healthy subjects received
either atorvastatin calcium (10 mg once a day) or simvastatin (20 mg once
a day) for the first 14 days of the study. Nelfinavir (1,250 mg twice a day
) was added on days 15 to 28. Pharmacokinetic assessment was performed on d
ays 14 and 28. The study drugs were well tolerated. Nelfinavir increased th
e steady-state area under the plasma concentration-time curve during one do
sing period (AUC(tau)) of atorvastatin 74% and the maximum concentration (C
-max) of atorvastatin 122% and increased the AUC(tau) of simvastatin 505% a
nd the Cu-max of simvastatin 517%. Neither atorvastatin nor simvastatin app
eared to alter the pharmacokinetics of nelfinavir. It is recommended that c
oadministration of simvastatin with nelfinavir should be avoided, whereas a
torvastatin should be used with nelfinavir with caution.