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ARTICLE | Distillery Techniques

Disease models; drug properties

Claire Quang
February 20, 2019 4:13 PM UTC

Rats expressing human UGT2 or CYP3A gene clusters could be used to predict the PK of drug compounds metabolized by the two enzyme families. Rats engineered to express the entire human UGT2 cluster, including UGT2 family polypeptide B15 (UGT2B15) and UGT2B17, recapitulated the metabolism kinetics of the UGT2 substrates Retrovir zidovudine and Lopid gemfibrozil observed in humans. Rats engineered to express the entire human CYP3A cluster, including CYP3A4 and CYP3A5, recapitulated the metabolism kinetics of the generic CYP3A substrates triazolam and midazolam and the plasma concentration-time profiles of triazolam and its metabolites observed in humans. Next steps could include testing additional UGT2 and CYP3A substrates in the rat models.

GlaxoSmithKline plc and Roche market Retrovir zidovudine to treat HIV/AIDS...

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