Steven Shafer

Publication Details

• Using the time of maximum effect site concentration to combine pharmacokinetics and pharmacodynamics.

  Minto CF, Schnider TW, Gregg KM, Henthorn TK, Shafer SL. Anesthesiology. 2003; 99 (2): 324-33

  To simulate the time course of drug effect, it is sometimes necessary to combine the pharmacodynamic parameters from an integrated pharmacodynamic-pharmacodynamic study (e.g., volumes, clearances, k(e0) [the effect site equilibration rate constant], C(50) [the steady state plasma concentration associated with 50% maximum effect], and the Hill coefficient) with pharmacokinetic parameters from a different study (e.g., a study examining a different age group or sampling over longer periods of time). Pharmacokinetic-pharmacodynamic parameters form an interlocked vector that describes the relationship between input (dose) and output (effect). Unintended consequences may result if individual elements of this vector (e.g., k(e0)) are combined with pharmacokinetic parameters from a different study. The authors propose an alternative methodology to rationally combine the results of separate pharmacokinetic and pharmacodynamic studies, based on t(peak), the time of peak effect after bolus injection.

  PubMedID: 12883405