BULITTA J, HORKOVICS-KOVATS S, BOREK M, SKOTT A, ILLAUER M, RODAMER M, KINZIG-SCHIPPERS M, SORGEL F; 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-1625.

IBMP, Nurnberg, Germany.

BACKGROUND: CLA's effects on drug metabolism have most recently received new interest (Pinto AG et al. Clin. Pharmacol. Ther. 73, PDI-C-6, 2003). METHODS: We dosed 24 healthy volunteers (12 males, 12 females; weight: 66.5+/-11.8 kg, age: 29+/-8 yrs, height 168+/-10 cm) for a total of 4 days with b.i.d. 500 mg CLA. CLA and its metabolite 14(R)-hydroxy-clarithromycin (CLA-MET) were analyzed by LC-MS/MS, pharmacokinetics was determined by non-compartmental methods, statistics by ANOVA. RESULTS: The method involves acetonitrile protein precipitation, reversed-phase HPLC and detection by LC-MS/MS (API 3000 Mass Spectrometer) with a SRM method as follows: Precursor product ion for CLA m/z 748.6 m/z 158.0, m/z 764.8 m/z 158.2 for CLA-MET and m/z 837.6 m/z 679.6 for internal standard (IS), positive mode. Under these conditions CLA, CLA-MET and IS were eluted after approximately 1.8, 0.8 and 2.0 minutes, respectively. The assay showed an excellent linearity from 0.00915-4.00 microg/mL (CLA) and 0.00917-3.98 microg/mL (CLA-MET). The inter-day precision/accuracy ranged from 3.5-6.2 % / <3.2 % for CLA and from 5.3-7.9 % / <3.0 % for CLA-MET. The intra-day precision/accuracy ranged from 2.5-7.6 % / <4.8 % for CLA and from 0.8-6.5 % / <7.2 % for CLA-MET. Values in the table are arithmetic mean +/- standard deviation or p-values from ANOVA: [table: see text]. CONCLUSIONS: CLA inhibits its own CYP3A metabolism early on (dose 3). The site and nature of inhibition (hepatic and/or intestinal CYP3A and/or P-glycoprotein) needs to be shown.

Publication Types:

• Meeting Abstracts

Keywords:

• Animals
• Chromatography, High Pressure Liquid
• Chromatography, Liquid
• Female
• Humans
• Male
• Mass Spectrometry
• metabolism
• pharmacokinetics

Other ID:

• GWAIDS0025382

UI: 102265006

From Meeting Abstracts