Journal of Southern Medical University ›› 2014, Vol. 34 ›› Issue (07): 1025-.
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Abstract: Objective To study the effects of carbamazepine on serum metabolic profiles in rats using nuclear magneticresonance (NMR) spectroscopy. Methods Twenty-four healthy male Wistar rats were randomized into 4 groups (n=6) for dailyintragastric administration of high-, medium- or low-dose carbamazepine or distilled water (control) for 7 days. Blood sampleswere collected from the abdominal aortic under anesthesia after the treatment to determine serum carbamazepineconcentration using high-performance liquid chromatography. 1H nuclear magnetic resonance (1H NMR) spectra wereacquired for pattern recognition analysis. Histopathological changes of the renal and liver tissues of the rats were alsoexamined. 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 groupsshowed renal pathologies. Compared with the control group, the high-dose carbamazepine group showed lowered serumconcentrations 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, andadipic acid. Principal component analysis revealed significant differences of the metabolites between carbamazepine-treatedgroups and the control group. The metabolic profiles showed no differences in the kinds of metabolites although theconcentrations of the metabolites varied between the carbamazepine groups. Conclusions Carbamazepine significantly affectsmetabolism 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.
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https://www.j-smu.com/EN/Y2014/V34/I07/1025