Impact of CYP2A6 gene polymorphism on the pharmacokinetics of dexmedetomidine for premedication.

BACKGROUND: Dexmedetomidine is a widely used sedative in clinic, which is mainly metabolized by cytochrome P450 2A6 (CYP2A6). Dexmedetomidine was rarely reported for off-label usage of premedication, but lacking relevant pharmacokinetic investigations. Therefore, our study determined the dexmedetomidine pharmacokinetics of CYP2A6*4 allele in Chinese patients pretreated with dexmedetomidine whose mutation frequency of CYP2A6*4 are high, in order to provide clinical references. METHODS: Thirty-one elective surgery patients received premedication with 0.5 µg/kg dexmedetomidine via intravenous pump. Their plasma concentrations at multiple time-points and polymorphism of CYP2A6*4 were determined and statistically analyzed. RESULTS: 9 patients were *1/*4 or *4/*4, and 22 patients were *1/*1. The main pharmacokinetic parameters were area under curve (AUC) 1396.19 ± 332.47h· ng· l-1, peak blood concentration (Cmax) 495.50 ± 104.90ng· l-1, distribution volume (V) 0.68 ± 0.20 L/kg, clearance (CL) 0.38 ± 0.11 L/h/kg, distribution half-life (t1/2α) 0.05 ± 0.01h, elimination half-life (t1/2ß) 2.53 ± 0.04h. No significant pharmacokinetic differences were found among CYP2A6*1/*1, *1/*4, and *4/*4 patients. CONCLUSIONS: In Chinese patients pretreated with dexmedetomidine, T1/2ß was consistent with that published, but T1/2α, V and Cl were lower. It was unnecessary to consider the mutation when developing the precision regimen of dexmedetomidine.

Evaluation of hepatoprotective effect of Zhi-Zi-Da-Huang decoction and its two fractions against acute alcohol-induced liver injury in rats.

AIM OF THE STUDY: To investigate the hepatoprotective effect of Zhi-Zi-Da-Huang decoction (ZZDHD) and its two fractions (one is extracted with diethyl ether as a solvent from the water extract and is called ZD-DE for short, the other is the remained aqueous fraction after extracted with diethyl ether and is abbreviated as ZD-AQ) against acute alcohol-induced liver injury in rats. MATERIALS AND METHODS: Animals were administered orally with alcohol 6g/kg at 2h after the doses of ZZDHD and two fractions everyday for eight consecutive days except rats in normal group. The protective effect was evaluated by biochemical parameters including aspartate transaminase (AST), alanine transferase (ALT), reduced glutathione (GSH), malondialdehyde (MDA) and superoxide dismutase (SOD). The biochemical observations were supplemented by histopathological examination. HPLC-UV was used for phytochemical analysis of the ZZDHD and its two fractions. RESULTS: The high dose of ZZDHD exhibited a significant protective effect by reversing the biochemical parameters and histopathological changes. ZD-DE and ZD-AQ demonstrated different protective action in biochemical examination. Partly assayed indexes were ameliorated after administrated the media dose of ZZDHD. HPLC analysis indicated that ZZDHD contained flavonoids, anthraquinones and iridoids, which might be the active chemicals. CONCLUSIONS: This study demonstrated the hepatoprotective activity of ZZDHD thus scientifically supported the usage of this formula.