Study On In Vivo Activities Of CYP3A Enzyme In Bactrian Camel With Specific Probe Drug | 72202
Journal of Veterinary Science & Technology
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The aim of the research is to study the in vivo activities of Bactrian camels' CYP3A enzymes by investigating the
pharmacokinetic characteristics of CYP3A specific probe drug Midazolam in Bactrian camel, and the effect of Itraconazole
on the pharmacokinetic behavior of Midazolam was studied simultaneously. Firstly, five healthy adult Bactrian camels were
intramuscularly injected with the single dose of 0.1 mg/kg Midazolam, and then blood samples were collected from the jugular
vein at different time following the administration. Secondly, after 7 days drug clearance period, these five experimental
camels were injected intramuscularly with the single dose of 0.1 mg/kg Itraconazole for 4 consecutive days, and following 2
h of last injection, Bactrian camels were administered intramuscularly with the single dose of 0.1 mg/kg Midazolam again.
Blood samples were collected by same route and same intervals as previous, and the plasma was separated by centrifugation.
The plasma concentration of Midazolam was determined high performance liquid chromatography-UV detection, and
the pharmacokinetic parameters of Midazolam were analyzed by WinNonLin 7.0 with non-compartmental model. The
pharmacokinetic parameters of Midazolam in group probe drug only and in group enzyme inhibitor plus probe drug were
as follows: the T1/2 was 2.5±0.073 h and 3.674±0.29 h, Tmax was 0.85±0.09 h and 0.54±0.06 h, Cmax was 0.62±0.12 μg/mL and
0.80±0.06 μg/mL, AUC0-t was 1.47±0.35 h•μg/mL and 2.15±0.15 h•μg/mL, Vd was 259.17±41.29 mL/kg and 152.09±22.49 mL/
kg, CL was 53.46±14.25 mL/h/kg and 34.3±5.13 mL/h/kg, and MRT was 3.71±0.16 h and 4.60±0.52 h, respectively. Therefore, all
the T1/2, Tmax, Cmax and MRT of Midazolam in Bactrian camels were relatively low which indicated that Bactrian camels' CYP3A
enzyme possess high activity on metabolism of Midazolam. Furthermore, the CYP3A enzyme was significantly inhibited by
Itraconazole which can increase the T1/2, Cmax, AUC and MRT, and can reduce the Tmax of Midazolam in Bactrian camel.
Surong Hasi is currently working as a professor in college of veterinary medicine, inner mongolia agricultural university, and is a director of camel protection association of Inner Mongolia. His research interests are mainly focused on the pharmacokinetic characteristics of veterinary drugs in different species, drug-drug interactions in animals, pharmacological activities of camel milk and Bactrian camel CYP enzymes.
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