Influence of aprepitant on the pharmacodynamics and pharmacokinetics of gliclazide in rats and rabbits

PeerJ
Raghunandan Reddy KuraMastan Shaik

Abstract

Concomitant drug administration is a general phenomenon in patients with chronic diseases such as diabetes mellitus. Among the currently available oral antidiabetic drugs, gliclazide is a commonly prescribed drug considering its multiple benefits in diabetic patients. Aprepitant is a commonly prescribed antiemetic drug which is mainly metabolized by CYP3A4, reported to have modest inductive and inhibitory effects on CYP2C9 and CYP3A4, respectively. Since gliclazide is metabolized by CYP2C9 (major) and CYP3A4 (minor), it is very difficult to predict the influence of aprepitant and its metabolic interaction with gliclazide. Considering the complexity associated with the combination of aprepitant and gliclazide, this study was designed to evaluate the influence of aprepitant on the pharmacodynamics (PD) and pharmacokinetics (PK) of gliclazide in animal models. The PD interaction studies were conducted in both rodent (normal and alloxan-induced diabetic rats) and non-rodent (rabbits) animal models (n = 6) while the PK interaction study was conducted in normal rabbits (n = 6). An extrapolated human therapeutic oral dose of gliclazide, aprepitant and their combination were administered to rats and rabbits with 7 days washout between ...Continue Reading

References

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Citations

Sep 27, 2018·Experimental and Therapeutic Medicine·Chengjun SongZhihong Chen
Aug 1, 2019·World Journal of Diabetes·Nattachet PlengvidhyaPa-Thai Yenchitsomanus

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Methods Mentioned

BETA
ELISA

Software Mentioned

Phoenix WinNonlin

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