MONTAY G, CHEVALIER P, GUIMART C, GUILLAUME M, SHI J, BHARGAVA V; Interscience Conference on Antimicrobial Agents and Chemotherapy (43rd: 2003: Chicago, Ill.).

Abstr Intersci Conf Antimicrob Agents Chemother Intersci Conf Antimicrob Agents Chemother. 2003 Sep 14-17; 43: abstract no. A-1624.

Aventis, Vitry sur Seine, France.

BACKGROUND: Concomitant administration of simvastatin (SIM) and erythromycin (ERY) has been shown to increase bioavailability of SIM 6-fold (Clin Pharmacol Ther 1998;64:177-182). This open, non-randomized, repeated-dose study evaluated the magnitude of the pharmacokinetic (PK) interaction between standard doses of SIM and clarithromycin (CLA). METHODS: Twelve healthy adult males received a single dose of SIM 40 mg on Day 1, followed by CLA 500 mg twice daily (morning and evening, 12-h intervals) on Days 2-8. A further dose of SIM was administered concomitantly with the morning dose of CLA on Day 8 (evening dose of CLA administered 12 h later). Plasma samples were collected for up to 24 hours post dosing (Days 1 and 8) for assay of SIM and its active metabolite SIM acid. RESULTS: Compared with SIM alone, coadministration of CLA and SIM significantly increased both C[max] and AUC[(0-z)] for SIM by approximately 8-fold (p<0.0001). Levels of SIM acid were also significantly (about 14-fold) higher during CLA treatment compared with SIM alone (p<0.0001). CLA had no significant effect on elimination of SIM or SIM acid. Both study treatments were well tolerated. [table: see text]. CONCLUSIONS: A standard dosing regimen of CLA significantly increases the plasma levels of SIM and SIM acid. The magnitude of interaction is considerably higher than that published with ERY, but the lesser frequency of dosing with CLA (twice daily dosing vs three or four-times daily for ERY) may represent an advantage of CLA over ERY.

Publication Types:

• Meeting Abstracts

Keywords:

• Adult
• Area Under Curve
• Biological Availability
• Clarithromycin
• Drug Interactions
• Erythromycin
• Humans
• Male
• Simvastatin
• pharmacokinetics

Other ID:

• GWAIDS0025374

UI: 102264998

From Meeting Abstracts