HSYU PH, LEWIS RH, SCHULTZ MD, LILLIBRIDGE JH, KERR BM; Interscience Conference on Antimicrobial Agents and Chemotherapy.
Abstr Intersci Conf Antimicrob Agents Chemother Intersci Conf Antimicrob Agents Chemother. 2000 Sep 17-20; 40: 14.
Agouron Pharmaceuticals, Inc., La Jolla, CA
BACKGROUND: Simvastatin (Zocor) and atorvastatin (Lipitor) are HMG-CoA reductase inhibitors, which are used to lower LDL cholesterol and triglycerides and to increase HDL cholesterol. Nelfinavir (VIRACEPT) is a common component of HAART. CYP3A4 is the major enzyme for the metabolism of simvastatin and atorvastatin and is inhibited by nelfinavir in humans. When simvastatin or atorvastatin is co-administered with nelfinavir, drug interaction may occur and warrants clinical evaluation.METHODS: Thirty-two subjects received either 10 mg atorvastatin QD or 20 mg simvastatin QD for the first 14 days of the study. Nelfinavir (1250 mg BID) was added from days 15 to 28. Pharmacokinetic assessment was performed on days 14 and 28. HMG-CoA reductase inhibitory activity (statin acids and their active metabolites), and plasma concentration of nelfinavir and its active metabolite M8 were measured. Clin. lab tests, physical exams and adverse events were used to assess safety.RESULTS: Thirty-one subjects completed the study (15 in the atorvastatin and nelfinavir arm and 16 in the simvastatin and nelfinavir arm). Geometric mean (95% CI) values of simvastatin and atorvastatin are summarized as follows [table: see text]. Nelfinavir increased the AUC of simvastatin 506% and C[max] of simvastatin 517% and increased the AUC of atorvastatin 74% and C[max] of atorvastatin 122%. Neither atorvastatin nor simvastatin appeared to alter the pharmacokinetics of nelfinavir or M8. Nelfinavir in combination with atorvastatin or simvastatin was well tolerated during 14 days of co-administration. No serious or clinically significant AEs or laboratory abnormalities were observed. The presence of nelfinavir did not have an obvious impact on the lipid lowering effects of atorvastatin or simvastatin. Conclusion: Nelfinavir increases plasma concentrations of simvastatin, and to a lesser extent, atorvastatin. Concomitant use of nelfinavir with simvastatin is not recommended. Caution should be exercised in co-administering nelfinavir with atorvastatin.KEYWORDS: Drug interactions; Nelfinavir; Protease inhibitor
Publication Types:
Keywords:
- Area Under Curve
- Cholesterol, HDL
- Cholesterol, LDL
- Drug Interactions
- Heptanoic Acids
- Humans
- Hydroxymethylglutaryl CoA Reductases
- Hydroxymethylglutaryl-CoA Reductase Inhibitors
- Hydroxymethylglutaryl-CoA-Reductases, NADP-dependent
- Lipids
- Nelfinavir
- Pyrroles
- Simvastatin
- atorvastatin
- pharmacokinetics
Other ID:
UI: 102247412
From Meeting Abstracts