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Table 2 In vitro PK parameters

From: An integrated pharmacokinetics ontology and corpus for text mining

Experiment types Parameters Description Unit References
Single Drug Metabolism Experiment Km Michaelis-Menten constant. mg L-1 Segel p28.
  Vmax Maximum velocity of the enzyme activity. mg h-1 mg-1 protein Segel p19
  CLint Intrinsic metabolic clearance is defined as ratio of maximum metabolism rate, Vmax, and the Michaelis-Menten constant, Km. ml h-1 mg-1 protein RT p165
  Metabolic ratio Parent drug/metabolite concentration ratio NA  
  fmenzyme Fraction of drug systemically available that is converted to a metabolite through a specific enzyme. NA RT xiii
Single Drug Transporter Experiment Papp The apparent permeability of compounds across the monolayer cells. cm/sec Transport Consortium
  Re Re is the ratio of basolateral to apical over apical to basolateral. NA Transport Consortium
  Radioactivity Total radioactivity in plasma and bile samples is measured in a liquid scintillation counter dpm/mg protein Transport Consortium
  Uptake Volume The amount of radioactivity associated with the cells divided by its concentration in the incubation medium. ul/mg protein Transport Consortium
Drug Interaction Experiment IC50 Inhibitor concentration that inhibits to 50% of enzyme activity. mg L-1  
  Ki Inhibition rate constant for competitive inhibition, noncompetitive inhibition, and uncompetitive inhibition. mg L-1 Segel p103
  Kdeg The natural degradation rate constant for the Enzyme. h-1 Rostami-Hodjegan and Tucker
  KI The concentration of inhibitor associated with half maximal Inactivation in the mechanism based inhibition. mg L-1 Rostami-Hodjegan and Tucker
  Kinact The maximum degradation rate constant in the presence of a high concentration of inhibitor in the mechanism based inhibition. h-1 Rostami-Hodjegan and Tucker
  Emax Maximum induction rate Unit free Rostami-Hodjegan and Tucker
  EC50 The concentration of inducer that is associated with the half maximal induction. mg L-1 Rostami-Hodjegan and Tucker
Type of Drug Interactions Competitive inhibition, noncompetitive inhibition, uncompetitive inhibition, mechanism based inhibition, and induction. Rostami-Hodjegan and Tucker   
  1. Note: Segel H. Irwin. Enzyme Kinetics - Behavior and analysis of rapid equilibrium and steady state enzyme systems. John Wiley & Sons, Inc. 1975, New York. Rostami-Hodjegan Amin and Tucker Geoff ‘In silico’ simulations to assess the ‘in vivo’ consequences of ‘in vitro’ metabolic drug-drug interactions. Drug Discovery Today, 2004, 1, 441-448. The International Transporter Consortium, Membrane transporters in drug development. Nature Review Drug Discovery, 9, 215-236. Rowland Malcolm and Tozer N. Thomas Clinical Pharmacokinetics Concepts and Applications, 3rd edition. 1995, Lippincott Williams & Wilkins.