| The Bactrian Camel is one of the most unique mammals on the planet and has adapted perfectly to life in the Gobi desert where food and water can often be scarce,and the temperature changes rapidly from the scorching-hot days to the cooler nights.Bactrian camels like to eat plants with a few protein content and rich cellulose,as well as like the plants with high salinity and salty content.And this unique eating behavior was closely related to Bactrian camel’s CYP enzymes.CYP enzymes play critical roles in the first pass metabolism of endobiotics and xenobiotic compounds,many of which are toxic and carcinogentic.CYP1A is one of the principal CYPs expressed in liver,and participates extensively in drug oxidations.This experiment was carried out to study in vivo activities of Bactrian camel CYP1A enzyme and the influence ofspecific enzyme inhibitor on the CYP1A enzyme.Firstly,the camels were randomly divided into two groups which of group probe drug only and group enzyme inhibitor plus probe drug,respectively.And then a crossover design was carried out in two experimental periods following 15 days of drug clearance period.Each camel(n=6)in group probe drug only was intramuscularly administered the Acetaminophen at a dosage of4 mg/kg body weight.And each camel in group enzyme inhibitor plus probe drug was intramuscularly administered Lomefloxacin at a dosage of 0.4 mg/kg for 4 continuous days,and then intramuscularly administered the Acetaminophen at a dosage of 4 mg/kg body weight.The blood samples were collected at different time intervals following the administration of Acetaminophen,and the plasma was separated for determination of drug concentration.Secondly,the dynamic concentration of Acetaminophen in Bactrian camel plasma was determined by the reversed phase high-performance liquid chromatography(RP-HPLC)for exploring the in vivo activities of Bactrian camel CYP1Aenzyme following the samples’ protein was precipitated by methanol directly.The internal standard was meta-Acetaminophen,the mobile phase was composed of methanol-water(20/80),the flow rate was 0.5 μg/mL,and the detection wavelength was 248 nm.The results showed that retention time of para-Acetaminophen and meta-Acetaminophen was 6.5 min and 9.2 min,respectively,and was not disturbed by other miscellaneous peaks.The calibration curve was well linearity in the range of 0.08 to 10.24 μg/mL(r2= 0.9997,and the quantitation limit of Acetaminophen was 0.08 μg/mL.Both the inter-day and intra-day RSD were under 7%,the absolute and relative recovery was 80.00%to 93.00%and94.00%to 103.00%,respectively.The pharmacokinetic parameters of para-Acetaminophen were calculated by WinNonLin 7.0.The pharmacokinetic parameters of Acetaminophen in group probe drug only and in group enzyme inhibitor plus probe drug were as follow:elimination half-life(TI/2)was 5.59±0.17 h and 6.24±0.25 h,time to peak concentration(Tmax)was 1.70±0.51 h and0.833±0.37 h,maximum plasma concentration of(Cmax)was 0.96±0.43 μg/mL and 1.22±0.66 μg/mL,the area under the curve(AUC0-t)was 5.83±0.31 μg·h/mL and 8.88±0.23 μg·h/mL,apparent volume of distribution(Vd)was 4416.81±138.23 mL/kg and 3934±90.03 mL/kg,clearance(CL)was 593.04±28.41mL/h/kgand 437.05±12.63 mL/h/kg,mean residence time(MRT)was 6.37±0.56 h and 6.98±0.63 h,respectively.Therefore,the specific probe substrate of CYP1A enzyme-Acetaminophen was rapid absorbed and eliminated slowly in Bactrian camels.And the CYP1A enzyme was significantly inhibited by Lomefloxacin which can markedly increase the T1/2,Cmax,AUC and MRT and reduce the Tmax of Acetaminophen in Bactrian camel... |
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