Determination of serum carbamazepine concentration and metabonomic analysis in rats / 南方医科大学学报

ABSTRACT

<p><b>OBJECTIVE</b>To study the effects of carbamazepine on serum metabolic profiles in rats using nuclear magnetic resonance (NMR) spectroscopy.</p><p><b>METHODS</b>Twenty-four healthy male Wistar rats were randomized into 4 groups (n=6) for daily intragastric administration of high-, medium- or low-dose carbamazepine or distilled water (control) for 7 days. Blood samples were collected from the abdominal aortic under anesthesia after the treatment to determine serum carbamazepine concentration using high-performance liquid chromatography. ¹H nuclear magnetic resonance (¹H NMR) spectra were acquired for pattern recognition analysis. Histopathological changes of the renal and liver tissues of the rats were also examined.</p><p><b>RESULTS</b>Steady-state blood concentration of carbamazepine in high-, medium- and low-dose groups were 14.64 ± 1.41, 8.54 ± 1.19, and 4.56 ± 0.64 µg/ml, respectively. Slight liver swelling was found in high-dose group, but none of the groups showed renal pathologies. Compared with the control group, the high-dose carbamazepine group showed lowered serum concentrations of 1,3-diaminopropane, deoxycorticosterone, 7-dehydrocholesterol, betaine, beta-alanine, L-cystathionine, 4-methyl-2-oxovaleric acid, and creatine with increased levels of saccharides, lactate, succinic acid, acetyl phosphate, and adipic acid. Principal component analysis revealed significant differences of the metabolites between carbamazepine-treated groups and the control group. The metabolic profiles showed no differences in the kinds of metabolites although the concentrations of the metabolites varied between the carbamazepine groups.</p><p><b>CONCLUSIONS</b>Carbamazepine significantly affects metabolism in normal rats. This finding provides evidence for clinical drug monitoring and drug safety of carbamazepine. NMR technique has important values for pharmacodynamic and toxicological evaluation of drugs.</p>