Christoph Funk

Learn More
BACKGROUND During clinical trials bosentan, the first orally active endothelin receptor antagonist, caused asymptomatic transaminase elevations in some patients. In this study we investigated whether inhibition of the hepatocanalicular bile salt export pump (rodents, Bsep; humans, BSEP ABCB11) could account for bosentan-induced liver injury. METHODS We(More)
Hepatic uptake carriers of the organic anion-transporting peptide (OATP) family of solute carriers are more and more recognized as being involved in hepatic elimination of many drugs and potentially associated drug-drug interactions. The gemfibrozil-statin interaction was studied at the level of active hepatic uptake as a model for such drug-drug(More)
Troglitazone is a thiazolidinedione insulin sensitizer drug for the treatment of type 2 non-insulin-dependent diabetes mellitus (NIDDM). Based on an increasing number of reports on troglitazone-associated liver toxicity, the cholestatic potential of troglitazone has been investigated. Rapid and dose-dependent increases in the plasma bile acid concentrations(More)
Troglitazone is a thiazolidinedione insulin sensitizer drug for the treatment of type 2 non-insulin-dependent diabetes mellitus (NIDDM). Based on an increasing number of reports on troglitazone-associated liver toxicity, the cholestatic potential of troglitazone and its major metabolite troglitazone sulfate has been investigated. In isolated perfused rat(More)
The use of in vitro data for quantitative predictions of transporter-mediated elimination in vivo requires an accurate estimation of the transporter Michaelis-Menten parameters, V(max) and K(m), as a first step. Therefore, the experimental conditions of in vitro studies used to assess hepatic uptake transport were optimized regarding active transport(More)
BACKGROUND Hepatic drug transporters of the solute carrier (OATPs, OAT2, OCT1, NTCP) and ABC transporter superfamilies (MDR1, MRPs, BCRP, BSEP) can significantly modulate drug ADME routes. OBJECTIVE The currently available literature was reviewed with focus on hepatic drug transporters, related drug-drug interactions and available tools for transporter(More)
A mechanistic model was applied to quantitatively derive the kinetic parameters from in vitro hepatic uptake transport data. These parameters were used as input to simulate in vivo elimination using a fully mechanistic physiologically based pharmacokinetic (PBPK) model. Fexofenadine and napsagatran, both BDDCS class 3 drugs, were chosen as model compounds.(More)
Drug-induced liver injury (DILI) is a leading cause of acute hepatic failure and a major reason for market withdrawal of drugs. Idiosyncratic DILI is multifactorial, with unclear dose-dependency and poor predictability since the underlying patient-related susceptibilities are not sufficiently understood. Because of these limitations, a pharmaceutical(More)
The aim of this study was to evaluate a physiologically based pharmacokinetic (PBPK) model for predicting PK profiles in humans based on a model refined in rats and humans in vitro uptake-transport data using valsartan as a probe substrate. Valsartan is eliminated unchanged, mostly through biliary excretion, both in humans and rats. It was, therefore,(More)
The aim of this study was to evaluate a strategy based on a physiologically based pharmacokinetic (PBPK) model for the prediction of PK profiles in human using in vitro data when elimination of compounds relies on active transport processes. The strategy was first applied to rat in vivo and in vitro data in order to refine the PBPK model. The model could(More)