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Antimicrobial Agents and Chemotherapy, December 2001, p. 3445-3450, Vol. 45, No. 12
0066-4804/01/$04.00+0   DOI: 10.1128/AAC.45.12.3445-3450.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

Pharmacokinetic Interactions between Nelfinavir and 3-Hydroxy-3-Methylglutaryl Coenzyme A Reductase Inhibitors Atorvastatin and Simvastatin

Poe-Hirr Hsyu,* Melissa D. Schultz-Smith, James H. Lillibridge, Ronald H. Lewis, and Bradley M. Kerr

Agouron Pharmaceuticals Inc., A Pfizer Company, La Jolla, California

Received 8 January 2001/Returned for modification 24 July 2001/Accepted 14 September 2001

3-Hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors are effective agents in lowering cholesterol and triglycerides and are being used by human immunodeficiency virus-positive patients to treat the lipid elevation that may be associated with antiretroviral therapy. Many HMG-CoA reductase inhibitors and protease inhibitors are metabolized by the same cytochrome P450 enzyme 3A4 (CYP3A4). In addition, many protease inhibitors are potent 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 and 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 days 14 and 28. The study drugs were well tolerated. Nelfinavir increased the steady-state area under the plasma concentration-time curve during one dosing period (AUCtau ) of atorvastatin 74% and the maximum concentration (Cmax) of atorvastatin 122% and increased the AUCtau of simvastatin 505% and the Cmax of simvastatin 517%. Neither atorvastatin nor simvastatin appeared to alter the pharmacokinetics of nelfinavir. It is recommended that coadministration of simvastatin with nelfinavir should be avoided, whereas atorvastatin should be used with nelfinavir with caution.

* Corresponding author. Mailing address: Agouron Pharmaceuticals Inc., A Pfizer Company, Clinical Pharmacology, 11085 Torreyana Rd., San Diego, CA 92121. Phone: (858) 622-7465. Fax: (858) 678-8293. E-mail: poe.hsyu{at}agouron.com.

Antimicrobial Agents and Chemotherapy, December 2001, p. 3445-3450, Vol. 45, No. 12
0066-4804/01/$04.00+0   DOI: 10.1128/AAC.45.12.3445-3450.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.


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