Comparation Of Hedatic Microsomal Metabolism And Bioavailability Between Different Coenzyme Q₁₀ In Rats And Besgle Dogs

Coenzyme Q10has a fundamental role in cellular bioenergetics and is also an important antioxidant. Potential benefits of CoQ10supplementation have been recognized with particular reference to cardiovascular and neurodegenerative diseases. Coenzyme Q10is an endogenous compound that exists in two redox forms, namely ubiquinone(CoQ10) and ubiquinol(CoQ10H2), which also includes both morphous (crystal) and amorphous (powder). This thesis focused on the bioavailability of different Coenzyme Q10. We compared the metabolism of CoQ10in liver microsomes obtained from different species to find which species microsome had the similar metabolic characteristics with human liver microsome(HLM). Then, bioavailability of different CoQ10(crystal, powder of oxidized form or reduced form) was studied in rats and dogs.1Metabolism of Coenzyme Q10in different species liver microsomesObjectives To compare the metabolism of CoQ10in different species microsomes, so as to find which species microsome had the similar metabolic characteristics with HLM. The result was used in choosing the right species for the in vivo studies.Methods CoQ10was incubated in different species microsomes and the metabolic characteristics were measured by substrate depletion and the metabolism-time curve. Results Dog liver microsome(DLM) had the most similar metabolic characteristics with HLM, followed by rat liver microsome (RLM). And there was a larger difference between Mouse liver microsome(MLM) and HLM.Conclusion DLM and RLM had similar metabolic characteristics with HLM, suggesting that the metabolism in rats and Beagle dogs may predict the metabolism of CoQ10in human body.2Bioavailability of different Coenzyme Q10in RatsObjectives To compare the bioavailability of different CoQ10(crystal, powder of oxidized form or reduced form) in rats.Methods A rapid and sensitive method for the determination of CoQ10in rat plasma was developed using LC-MS/MS. CoQ10concentration were determined in plasma at different times after oral administration. Then the concentration-time curve and pharmacokinetic parameters were obtained.Results The calibration curve has good linear with R2=0.9996for CoQ10. Recoveries ranged from82.0%to91.5%, RSD≤12.4%. Matrix effect ranged from99.8%to106.1%, RSD≤5.7%.The average accuracy ranged from95.0%to101.5%, RSD of both the intra-and inter-day precisions≤8.8%. After oral administration of crystal or powder of oxidized form, the CoQ10AUC0-t were315.1±72.6and178.4±95.4μg/L×h, respectively. After oral administration of crystal or powder of reduced form, the CoQio AUC0-t were967.4±486.2and746.4±195.8μg/L×h, respectively;Conclusion For both reduced form and oxidized form of CoQ10, the bioavailability of crystal was higher than powder in rats.3Bioavailability of different Coenzyme Q10in Beagle DogsObjectives To compare the bioavailability of different CoQ10(crystal, powder of oxidized form or reduced form) in beagle dogs. Methods A rapid and sensitive method for the determination of CoQ10in rat plasma was developed using LC-MS/MS. CoQ10concentration were determined in plasma at different times after oral administration. Then the concentration-time curve and pharmacokinetic parameters were obtained.Results The calibration curve has good linear with R2=0.9999for CoQ10. Recoveries ranged from88.3%to91.1%, RSD≤4.9%. Matrix effect ranged from98.4%to103.3%, RSD≤4.5%.The average accuracy ranged from98.6%to105.8%, RSD of both the intra-and inter-day precisions≤7.5%. After oral administration of crystal or powder of oxidized form, the CoQ10AUC0-t were3415.3±3261.7and1520.7±953.4μg/L×h respectively; After oral administration of crystal or powder of reduced form, the CoQ10AUC0-t were8223.6±1849.1and3269.0±626.0μg/L×h respectively;Conclusion For both reduced form and oxidized form of CoQ10, the bioavailability of crystal was higher than powder in beagle dogs.