The PPS encompasses all scientific analyses related to pharmacology, once the specimen has been collected and stored. There is a multi-step process to evaluate how the drug is being handled by the body after administration. The first step is to measure the drug concentrations longitudinally. This step is performed by the CPP’s Bioanalytical Unit:
Bioanalytical Unit
The Bioanalytical Section of the CPP is responsible for the measurement of drug concentrations in samples, either clinical or nonclinical. The Bioanalytical facility contains 5 triple-quadrupole mass spectrometers (MS/MS) with ESI/APCI sources, each with ultra-performance liquid chromatography (LC) systems that is used for organic, small molecule therapeutics. The Bioanalytical facility also has an inductively-coupled plasma mass spectrometer (ICP-MS) for quantitative inorganic/elemental analysis (e.g. cisplatin, oxaliplatin, carboplatin). Additionally, the Bioanalytical Section can develop and validate ligand-binding assays (e.g. ELISA) for the measurement of biologics and macromolecules.
All bioanalytical assays are developed and validated per FDA and ICH guidance for method validation, with FDA bioanalytical reports available upon request to support NDA submissions.
Clinical Pharmacokinetics and Pharmacometrics Unit
Once drug concentrations are measured in all samples from a PK study (clinical or nonclinical), step 2 is the pharmacokinetic (PK) analysis for the drug(s) of interest in a particular study. The PPS can analyze PK data using compartmental and non-compartmental approaches, as well as population modeling and simulation. The PPS uses PK software that is validated per FDA 21 CFR Part 11 regulations for non-compartmental (NCA) and can provide PK data in CDISK (either SEND or SDTM) format and reports for IND and NDA/ANDA submissions. Additionally, support for pharmacokinetic-pharmacodynamic (PK/PD) modeling and simulation of investigational agents or combination therapies to predict exposure-response in future trials, food effect analysis, and concentration-QT effect for new anticancer agents (Pharmacometrics).
Preclinical Pharmacology Unit
The PPS is also open to collaboration for new anticancer agents that are being introduced into preclinical models and can develop bioanalytical assays to quantitate and characterize preclinical drug metabolism and pharmacokinetics in preclinical models. The Preclinical Pharmacology Unit within the PPS specializes in bioanalytical assay development, validation and bioanalysis of pharmacokinetic samples from animal models of any specimen type (whole blood, plasma, serum, urine, heart, liver, lung, kidney, bone, tumor, etc.). From this PK data, this unit can apply mathematical models to preclinical data to inform future clinical trial design for that compound/drug, including optimal PK sampling times and dosing routes, amounts and frequencies. We have experience performing PK in mice, rats, woodchucks, rabbits, pigs, dogs, and monkeys, ranging from traditional oral or intravenous routes, to more novel techniques such as trans-arterial chemo-embolization in liver for local delivery of drug. We can measure any drug or compound type, ranging from inorganic or metal compounds (e.g., platinum) to organic small molecules, monoclonal antibodies, and antibody-drug conjugates. Additionally, the Preclinical Pharmacology Unit can develop formulations of new chemical entities and characterize protein binding, in vitro metabolism and transport, in vitro and in vivo (animal) drug-drug interactions, and bioequivalence (new formulations, food effect studies, etc.) studies in animals.
Questions? Contact Keith Schmidt, keith.schmidt@nih.gov
W: 240-858-3208
M: 301-204-5350