Quantifying Pharmacokinetics
There is a causal relationship between dose, dosage regimen, exposure of drug and its therapeutic benefit and adverse effects (1). To quantify pharmacological and toxicological effects of a drug or a molecule (e.g. Efficacy = Emax or Imax; Potency =EC50 or IC50) based on dose and effect, it is essential to quantify its pharmacokinetics. Quantifying PK helps in…
Volume of distribution and Clearance are fundamental Pharmacokinetic Parameters
Volume of distribution (V) and Clearance (CL) are fundamental pharmacokinetic (PK) parameters that determine the PK properties of a molecule. V is dependent on the physico-chemical properties and affinity of binding to tissues and the CL is dependent on the concentration, blood flow and biochemical mechanism of elimination of the molecule. V is predicted using…
The ONCOME could determine the Pharmacodynamics (Efficacy) of Anti-Cancer Drugs
Chemotherapy with targeted drugs in cancer is based on the presence of the abnormally expressed drug target (driver mutations that result in altered receptors or enzymes, or overexpression of the target) leading to dysregulation of biochemical signaling pathways and development of a cancer. The hypothesis is that when this abnormally expressed target is inhibited by…
Progression Free Survival In Humans Cancer Therapy: Can It Be PredictedFrom Mouse Models?
The primary clinical endpoint used for measuring the efficacy of an anti-cancer therapy is Progression Free Survival (PFS) or Overall Survival (OS). In preclinical (Nonclinical) pharmacology studies the mouse models of cancer form the basis for evaluating efficacy of anticancer therapies. The models include, with increasing degree of complexity, the Xenograft, Orthotopic, Syngeneic, Genetically Engineered…
Prediction of Human Pharmacokinetics and Estimation of First Time in Human Dose
For any drug discovery company, a major milestone is the administration of the clinical drug candidate for the first time in humans. The management, Project members including the pharmacometricians in particular wait anxiously to see how the first patient reacts to the first dose (potential adverse effects) and what the PK of the CD will…
Evaluation of Pharmacokinetic-Pharmacodynamic (PK/PD) Relationships of Anti-Bacterial Agents in Preclinical Models of Infection
Ramesh Jayaraman Director DoseQuantics Consulting INTRODUCTION The pharmacokinetics (time course of concentration in the body) of a drug when combined with its pharmacodynamics (onset, intensity, duration of pharmacological effect of the drug) determines the therapeutic potential of a drug (1). For an anti-bacterial drug or molecule, the primary measures of in vitro potency and efficacy…