A5015581560- Drug Transport and Resistance Mechanisms
- Pharmacological Effects and Toxicity Studies
- Biosimilars and Bioanalytical Methods
- Pregnancy and Medication Impact
- Protein purification and stability
- Pharmacogenetics and Drug Metabolism
- Drug-Induced Hepatotoxicity and Protection
- Antibiotics Pharmacokinetics and Efficacy
- Monoclonal and Polyclonal Antibodies Research
Roche (Switzerland)
2014-2017
Hepatic uptake carriers of the organic anion-transporting peptide (OATP) family solute are more and recognized as being involved in hepatic elimination many drugs potentially associated drug-drug interactions. The gemfibrozil-statin interaction was studied at level active a model for such Active, temperature-dependent fluvastatin into primary human hepatocytes shown. Multiple transporters this Chinese hamster ovary or HEK293 cells expressing either OATP1B1 (<i>K</i><sub>m</sub> = 1.4–3.5...
The use of in vitro data for quantitative predictions transporter-mediated elimination vivo requires an accurate estimation the transporter Michaelis-Menten parameters, V(max) and K(m), as a first step. Therefore, experimental conditions studies used to assess hepatic uptake transport were optimized regarding active processes, nonspecific binding, passive diffusion (P(dif)). A mechanistic model was developed analyze accurately describe these processes. This two-compartmental parameterized...
The multidrug resistance protein 1 (MDR1) is known to limit brain penetration of drugs and play a key role in drug-drug interactions (DDIs). Theoretical cut-offs from regulatory guidelines are used extrapolate MDR1 vitro vivo. However, these do not account for interlaboratory variability. Our aim was calibrate our experimental system allow better vivo predictions. We selected 166 central nervous (CNS) non-CNS the transport screening assay using Lewis lung cancer porcine kidney epithelial...
Monoclonal antibodies (mAbs) are a rapidly growing drug class for which great efforts have been made to optimize certain molecular features achieve the desired pharmacokinetic (PK) properties. One approach is engineer interactions of mAb with neonatal Fc receptor (FcRn) by introducing specific amino acid sequence mutations, and assess their effect on PK profile in vivo studies. Indeed, FcRn protects mAbs from intracellular degradation, thereby prolongs antibody circulation time plasma...