In Vitro DMPK

Toxicokinetic and pharmacokinetic studies are necessary before exposing humans to new investigational drugs in clinical trials. In vitro metabolism and plasma protein binding assays can aid non-clinical safety evaluation and justify starting dose and potential dose escalation steps. In vitro investigations of drug-drug interactions related to CYP enzymes are strongly recommended to guide participant selection, concomitant medications, and exclusion criteria. Package From Candidate To Clinics Toxicokinetic link to Bioanalysis/Toxciokinetics and pharmacokinetic studies are required prior to exposing human subjects to a new investigational drug in the first in human (FiH) clinical trial. We offer to determine the in vitro metabolism to either support or confirm the selection of appropriate toxicity species as well as the plasma protein binding of the drug candidate in human and animals in regulatory compliant assays to aid the non-clinical safety evaluation. If needed and depending on the availability of data at this stage, the latter can also be supported by relevant in vitro and/or in vivo PK studies, e.g., intrinsic clearance, PK in rodent/non-rodent species , enabling the prediction of human pharmacokinetics to justify starting dose and potential dose escalation steps in the FiH trial. In vitro investigations of drug-drug interactions (DDI) at least related to cytochrome P450 (CYP) enzymes are strongly recommended for FiH trials in patients to guide selection of participants, concomitant medications, and to define in- and exclusion criteria. Intrinsic Clearance The intrinsic hepatic clearance reflects the inherent ability of hepatocytes or other subcellular systems (e.g., microsomes, S9 fractions) to eliminate unbound drug and once corrected for non-specific binding in the incubation is governed solely by the activity of metabolizing enzymes. The use of in vitro metabolic clearance data from hepatocytes is a key approach to predict pharmacokinetics by in vitro-in vivo extrapolation (IVIVE) both in humans and animal species.