Simultaneously predict pharmacokinetic interaction of rifampicin with oral versus intravenous substrates of cytochrome P450 3A/P ‑glycoprotein to healthy human using a semi-physiologically based pharmacokinetic model involving both enzyme and transporter turnover.

Simultaneously predict pharmacokinetic interaction of rifampicin with oral versus intravenous substrates of cytochrome P450 3A/P‑glycoprotein to healthy human using a semi-physiologically based pharmacokinetic model involving both enzyme and transporter turnover. Eur J Pharm Sci. 2019 Apr 29;: Authors: Qian CQ, Zhao KJ, Chen Y, Liu L, Liu XD Abstract Several reports demonstrated that rifampicin affected pharmacokinetics of victim drugs following oral more than intravenous administration. We aimed to establish a semi-physiologically based pharmacokinetic (semi-PBPK) model involving both enzyme and transporter turnover to simultaneously predict pharmacokinetic interaction of rifampicin with oral versus intravenous substrates of cytochrome P450 (CYP) 3A4/P‑glycoprotein (P-GP) in human. Rifampicin was chosen as the CYP3A /P-GP inducer. Thirteen victim drugs including P-GP substrates (digoxin and talinolol), CYP3A substrates (alfentanil, midazolam, nifedipine, ondansetron and oxycodone), dual substrates of CYP3A/P-GP (quinidine, cyclosporine A, tacrolimus and verapamil) and complex substrates (S-ketamine and tramadol) were chosen to investigate drug-drug interactions (DDIs) with rifampicin. Corresponding parameters were cited from literatures. Before and after multi-dose of oral rifampicin, the pharmacokinetic profiles of victim drugs for oral or intravenous administration to human were predicted using the semi-PBPK model and compared...
Source: European Journal of Pharmaceutical Sciences - Category: Drugs & Pharmacology Authors: Tags: Eur J Pharm Sci Source Type: research