Introduction
The Pharmacokinetics group is involved in:
A) Synthetic NCEs: Development of validated bio-analytical assay procedures for quantification of NCEs in biological matrices, as per ICH guidelines, using HPLC and LC MS/MS
Evaluating important in-vitro DMPK parameters at the discovery phase so as to help in candidate selection, which include:
➤ Solubility; pKa; Log P
➤ GI stability under simulated gastric and simulated intestinal pH
➤ Plasma protein binding
➤ Whole Blood Partitioning / RBC uptake
➤ PAMPA/in-situ permeability
➤ Rat S-9/Microsomal Metabolic stability
➤ In-vitro metabolite profiling
B). Generating regulatory DMPK data to define drug metabolism and disposition, PK-PD correlation, PK-TK correlation, dose and dosage regimen at the preclinical development phase so as contribute in submission of IND applications to DCGI for the grant of permission to conduct human clinical trials; These studies include:
➤ In vivo oral and intravenous pharmacokinetic studies in at least one rodent and one non-rodent species
➤ Tissue distribution
➤ Metabolite profiling
➤ Excretion studies (urine, feces and bile)
➤ CYP 450 Reaction Phenotyping
➤ In-vitro metabolic studies with Human Recombinant CYPs
➤ Toxicokinetics (integrated with 28 day repeat dose toxicity studies in rats and monkeys)
C). Herbal Products: The group is involved in:
➤ Defining the finger print / pattern profile of various components of the preparation using validated LC MS/MS assay procedure
➤ Principle Component Analysis of pure marker components of the herbal preparations
➤ Development of bio-analytical procedure for the quantification of marker components in biological matrices for evaluating DMPK characteristics
➤ The group also undertakes work to define preclinical DMPK characteristics of multi-component herbal preparations based on the biologically active markers, which helps in taking them up to clinical trial level