Pharmacokinetics of metronidazole in rat blood, brain and bile studied by microdialysis coupled to microbore liquid chromatography.
Metronidazole is a synthetic nitroimidazole-derived antibacterial and antiprotozoal agent used for the treatment of infections involving gram-negative anaerobes. The aim of this study is to develop an in vivo microdialysis with microbore high-performance liquid chromatographic system for the pharmacokinetic study of metronidazole in rat blood, brain and bile. In addition, to investigate the disposition mechanism of metronidazole, the P-glycoprotein modulator and cytochrome P450 inhibitor were concomitantly administered. Separation of metronidazole from various biological fluids was applied to a microbore reversed-phase ODS 5 microm (150 x 1 mm I.D.) column. Its mobile phase consists of an acetonitrile-50 mM monosodium phosphate buffer (pH 3.0) containing 0.1% triethylamine (10:90, v/v) with a flow-rate of 0.05 ml/min. The UV detector wavelength was set at 317 nm. The results suggest that metronidazole penetrates the blood-brain barrier (BBB) and goes through hepatobiliary excretion. However, these pathways of BBB penetration and hepatobiliary excretion of metronidazole may not be related to the P-glycoprotein.
Tsai
Tung-Hu
TH
National Research Institute of Chinese Medicine, 155-1 Li-Nong Street Section 2, Shih-Pai, Taipei 112, Taiwan. thtsai@cma23.nricm.edu.tw
Chen
Yen-Fei
YF
D000818:Animals; D000890:Anti-Infective Agents / Q000097:blood / Q000493:pharmacokinetics*; D001646:Bile / Q000378:metabolism*; D001812:Blood-Brain Barrier; D001921:Brain / Q000378:metabolism*; D008297:Male; D008795:Metronidazole / Q000097:blood / Q000493:pharmacokinetics*; D017551:Microdialysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D012680:Sensitivity and Specificity
D000890:Anti-Infective Agents; D008795:Metronidazole