Journal of Steroid Biochemistry and Molecular Biology p. 183 - 192 (2016)
Update date:2022-08-17
Topics:
Ramakrishna, Rachumallu
Bhateria, Manisha
Singh, Rajbir
Bhatta, Rabi Sankar
16-dehydropregnenolone (DHP) is a promising novel antihyperlipidemic agent developed and patented by Central Drug Research Institute (CDRI), India. The purpose of the present study was to investigate whether DHP influences the activities and mRNA expression of hepatic drug-metabolizing cytochrome P450 (CYP) enzymes (CYP1A2, CYP2C11, CYP2D2, CYP2E1 and CYP3A1) in Sprague-Dawley (SD) rats. A cocktail suspension of CYP probe substrates which contained caffeine (CYP1A2), tolbutamide (CYP2C11), dextromethorphan (CYP2D2), chlorzoxazone (CYP2E1) and dapsone (CYP3A1) was administered orally on eighth- or fifteenth-day to rats pre-treated with DHP intragastrically at a dose of 36 and 72?mg/kg for one week and two weeks. The concentrations of probe drugs in plasma were estimated by liquid chromatography-tandem mass spectrometry (LC–MS/MS). Alongside, the effect of DHP on CYPs activity and mRNA expression levels were assayed in isolated rat liver microsomes and by real-time reverse transcription-polymerase chain reaction (RT-PCR), respectively. DHP had significant inducing effects on CYP1A2, 2C11, 2D2 and 2E1 with no effect on CYP3A1 in dose- and time-dependent manner, as revealed from the pharmacokinetic profiles of the probe drugs in rats. In-vitro microsomal activities and mRNA expression results were in good agreement with the in-vivo pharmacokinetic results. Collectively, the results unveiled that DHP is an inducer of rat hepatic CYP enzymes. Hence, intense attention should be paid when DHP is co-administered with drugs metabolized by CYP1A2, 2C11, 2D2 and 2E1, which might result in drug-drug interactions and therapeutic failure.
View MoreContact:+86-574-87065746
Address:10th Floor, No.787 Baizhang East Road,
Feiyang Biotechnology Co., Ltd.
Contact:+86-533-7866339
Address:Qilu Chemistry Park, 200m north of Management Community Building of Park
Tianjin Jiuri New Materials Co., Ltd.
Contact:+86-22-58889220
Address:C-5/6, Vison Hill, No.1 Gonghua Road, Huayuan Hi-tech Park, Tianjin, China.
Contact:021-36356756
Address:Room601,Building No.14,280 Yangcheng Road,Shanghai
Contact:0027-717-456976
Address:2ND FLOOR, 325 VAUSE ROAD, OVERPORT, 4001, SOUTH AFRICA
Doi:10.1002/aoc.4451
(2018)Doi:10.1002/aoc.4955
(2019)Doi:10.1039/c29710001384
(1971)Doi:10.1246/bcsj.58.3027
(1985)Doi:10.1039/c7nj02997g
(2017)Doi:10.1016/S1051-0443(07)61352-9
(1971)