Time of peak drug concentration after a single dose and a dose at steady state. 1997

H E Greenberg, and M J England, and E T Hellriegel, and T D Bjornsson
Department of Medicine, Jefferson Medical College, Thomas Jefferson University, Philadelphia, Pennsylvania 19107, USA.

The time of peak concentration after administration of oral drug is an often quoted and used pharmacokinetic parameter. It is not well appreciated, however, that the peak times after a single dose and a dose at steady state during a multiple administration regimen can differ significantly. This article derives the mathematical relationships that determine how a peak time at steady state differs from that after a single or first dose. These relationships are then evaluated using three different approaches: 1) graphic simulations of time courses of drug concentration for three hypothetical drugs; 2) comparisons of predicted and observed peak times using examples from the literature; and 3) comparisons of predicted and simulated peak times based on different sampling schedules for three hypothetical drugs. The key finding is that peak times after a dose at steady state can occur considerably earlier after administration than after a single dose. However, the manner by which peak times are usually determined, that is, the sampling time corresponding to the highest measured drug concentration, imposes significant limitations on the usefulness of this parameter.

UI MeSH Term Description Entries
D010599 Pharmacokinetics Dynamic and kinetic mechanisms of exogenous chemical DRUG LIBERATION; ABSORPTION; BIOLOGICAL TRANSPORT; TISSUE DISTRIBUTION; BIOTRANSFORMATION; elimination; and DRUG TOXICITY as a function of dosage, and rate of METABOLISM. LADMER, ADME and ADMET are abbreviations for liberation, absorption, distribution, metabolism, elimination, and toxicology. ADME,ADME-Tox,ADMET,Absorption, Distribution, Metabolism, Elimination, and Toxicology,Absorption, Distribution, Metabolism, and Elimination,Drug Kinetics,Kinetics, Drug,LADMER,Liberation, Absorption, Distribution, Metabolism, Elimination, and Response
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000284 Administration, Oral The giving of drugs, chemicals, or other substances by mouth. Drug Administration, Oral,Administration, Oral Drug,Oral Administration,Oral Drug Administration,Administrations, Oral,Administrations, Oral Drug,Drug Administrations, Oral,Oral Administrations,Oral Drug Administrations

Related Publications

H E Greenberg, and M J England, and E T Hellriegel, and T D Bjornsson
January 1980, Clinical pharmacokinetics,
H E Greenberg, and M J England, and E T Hellriegel, and T D Bjornsson
January 1992, Journal of pharmaceutical sciences,
H E Greenberg, and M J England, and E T Hellriegel, and T D Bjornsson
May 1999, European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V,
H E Greenberg, and M J England, and E T Hellriegel, and T D Bjornsson
January 1987, European journal of clinical pharmacology,
H E Greenberg, and M J England, and E T Hellriegel, and T D Bjornsson
October 1983, Journal of pharmaceutical sciences,
H E Greenberg, and M J England, and E T Hellriegel, and T D Bjornsson
January 1987, Clinical pharmacokinetics,
H E Greenberg, and M J England, and E T Hellriegel, and T D Bjornsson
March 2004, British journal of clinical pharmacology,
H E Greenberg, and M J England, and E T Hellriegel, and T D Bjornsson
January 1996, European journal of clinical pharmacology,
H E Greenberg, and M J England, and E T Hellriegel, and T D Bjornsson
November 1992, International journal of clinical pharmacology, therapy, and toxicology,
H E Greenberg, and M J England, and E T Hellriegel, and T D Bjornsson
January 1985, Clinical pharmacokinetics,
Copied contents to your clipboard!