Journal of Southern Medical University ›› 2014, Vol. 34 ›› Issue (07): 1025-.

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Determination of serum carbamazepine concentration and metabonomic analysis in rats

  

  • Online:2014-07-20 Published:2014-07-20

Abstract: Objective To study the effects of carbamazepine on serum metabolic profiles in rats using nuclear magnetic
resonance (NMR) spectroscopy. Methods 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. Results 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. Conclusions 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.