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Aim To develop a ultra-high performance liquid chromatography electrospray-ionization tandem mass spectrometry ( UPLC-MS/MS ) method for the simultaneous determination of salidroside derivative pOBz in rat plasma and brain tissue, and to study the pharmacokinetic profile and penetration of the blood-brain barrier in rats after a single dose intravenous administration of pOBz. Methods SD rats were administered pOBz at a dose of 50 mg • kg
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ObjectiveTo investigate the pharmacokinetic effects of baicalin on cerebral ischemia-reperfusion (I/R) after iv administration in rats.MethodsThe cerebral I/R rats were induced by occluding the bilateral carotid arteries of normal rats for 2 h,followed by reperfusion.The resultant animals were immediately iv administrated with baicalin (90 mg/kg),whilst the same dose of baicalin was injected to the normal rats.Plasma samples were collected at different time to construct pharmacokinetic profiles by plotting drug concentration vs time.Quantification of baicalin in rat plasma was achieved using a simple and rapid HPLC method.ResultsIn normal rats,the major parameters of distribution half-life,elimination half-life,area under the plasma concentration-time (AUC),apparent volume of distribution (Vd),and clearance (CL),estimated by an open two-compartmental model,were 0.8868 min,26.0968 min,149.6204 mg/min·L,4.765 L/kg,and 0.5776 L/kg·min),respectively.However,in I/R rats,the corresponding parameters were 2.084 min,34.4998 min,260.0188 μg.min/L,5.9376 L/kg,and 0.334 L/(kg·min),respectively.ConclusionThe cerebral I/R could significantly increase AUC and Vd values,decrease CL values,and prolong the terminal half-life of baicalin.These findings suggest that the injuries of I/R could play an important role in pharmacokinetic process ofbaicalin.
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PURPOSE: A plasma acetaminophen halflife of more than 4 hours has been correlated with hepatotoxicity in acetaminophen overdosing not treated with an antidote. However, the acetaminophen halflife has not been studied in patients receiving the antidote N-acetylcysteine (NAC). METHODS: Ninety-eight (98) patients with acetaminophen overdoses, all of whom were treated with N-acetylcysteine were studied. A minimum of 2 plasma acetaminophen valu e s > 2.0 microgram/ml were available for calculating the acetaminophen halflife, assuming first-order kinetics. RESULTS: Overall, the median acetaminophen halflife was 6.2 hours (range, 1.15~103.9 hours). Sixty-two (62) patients with no hepatotoxicity (AST 1,000 U/L) without acute hepatic failure, and 6 patients with hepatotoxicity (AST > 1,000 U/L) with hepatic failure had acetaminophen halflives of 3.7 hours (range, 1.15~23.2 hours), 5.9 hours (range, 1.96~26.2 hours), 6.3 hours (range, 2.19~15.38 hours), and 32.8 hours (range, 5.48~103.9 hours), respectively (p<0.05). A receiver operating characteristic curve analysis showed that an acetaminophen halflife of 5.19 hours provided better discrimination (sensitivity=69.6%, specificity=84.0%, accuracy=80.6%). CONCLUSION: The acetaminophen halflife correlates well with the degree of liver damage in patients treated with N-acetylcysteine. Longer halflives reflect a greater toxic effect on the liver.