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Physiologically based pharmacokinetics (PBPK) describes the pharmacokinetics (PK) of a drug by integrating its physicochemical and in vitro ADME properties (drug specific) with physiological parameters (system specific) of the body. This is known as the” bottom up” approach (mechanistic), the opposite of empirical description of PK (sum of exponentials/compartments) known as “top down” approach. The mechanistic…

Ramesh Jayaraman, DoseQuantics Consulting Pvt Ltd The strength of a PK model is evaluated by its ability to predict the behavior of the drug at a dose or regimen that is different from the dose for which the model was developed. When the model successfully predicts PK across dose levels or regimens its robustness and…

Physiologically based pharmacokinetics (PBPK) describes the pharmacokinetics (PK) of a drug by integrating its physicochemical and in vitro ADME properties (drug specific) with physiological parameters (system specific) of the body. This is known as the ”bottom up” approach (mechanistic), the opposite of empirical description of PK (sum of exponentials/compartments) known as “top down” approach. The…

Most often a Lead is determined based on meeting project criteria for But, a vital component seems to be missing in this set of criteria – Efficacy and PK/PD OR is not given importance. When all the above set criteria do not translate to efficacy (pharmacological effect/Pharmacodynamics) or safety, it suggests that there is no…

Ramesh Jayaraman, DoseQuantics Consulting, September 12th 2025 The true worth of an anti-cancer drug is measured not just by its ability to reduce the cancer burden aka objective response (reduction in tumor size, prevention of metastasis) but the relationship between the reduction in cancer burden and the increase in meaningful clinical benefit (increase in overall survival…

Ramesh Jayaraman, DoseQuantics Consulting Pvt Ltd. 7th September, 2025 Recently, two letters to the editors appeared in the journal Antimicrobial Agents Chemotherapy (1, 2) that discussed the merits of classification of anti-bacterial drugs as bacteriostatic and bactericidal. Spellberg et al observed that this classification is not correct and does not have clinical utility because there is no…

Drugs are combined to achieve a specific pharmacodynamic objective a) increase efficacy (eg cancer treatment) b)  reduce development of resistance (eg infection treatment) The choice of drugs to be combined to treat a specific disorder will depend on the drug-drug interactions at the pharmacokinetic level and at the pharmacodynamic level. There are a few approaches…

Clearance (CL) relates the rate of elimination of a molecule with its concentration in vivo. Many small molecules are cleared by enzymatic (metabolism) and transporter based mechanisms. Consequently,  molecules cleared by these mechanisms tend to display Michaelis-Menten (MM) or saturable (capacity dependent) kinetics. When concentrations are much below Km, CL is constant (Vmax/Km), exposures increase…