Ramesh Jayaraman DoseQuartics Consulting Steady state concentrations and accumulation Selection of dosing regimen is as important as dose for designing pharmacology and toxicology studies. The objectives of the pharmacology/toxicology studies could be based on answering specific questions such as Time to achieve steady state is determined by Volume of distribution and clearance. Steady state concentrations…
Ramesh Jayaraman DoseQuartics Consulting The Exposure (AUC) of a therapeutic when administered as infusions and bolus When a dose of a drug is administered as an intravenous bolus and as infusions of different durations, the exposures (AUC) will be the same in the dosing interval, under linear conditions. However, the peak concentrations achieved will decrease…
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 (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…
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…
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…
