Journal of Pharmacokinetics and Biopharmaceutics

, Volume 6, Issue 6, pp 539–546

Critical evaluation of the potential error in pharmacokinetic studies of using the linear trapezoidal rule method for the calculation of the area under the plasma level-time curve

  • Win L. Chiou

DOI: 10.1007/BF01062108

Cite this article as:
Chiou, W.L. Journal of Pharmacokinetics and Biopharmaceutics (1978) 6: 539. doi:10.1007/BF01062108


The linear trapezoidal rule method is commonly used for the estimation of the area under the plasma level-time curve. Error analyses are performed when the method is used in first-order absorption and first-order elimination kinetics in the one-compartment system. It is found that significant underestimations and overestimations in area during the absorption phase and postabsorption phase, respectively, can occur when the method is improperly used. During the exponential postabsorption phase the relative error is only a function of the ratio (n)of the time interval over the half-life of the two plasma data points in the interval. The error from the linear trapezoidal rule method at n=0.5 is about 1%. The error increases to 15.5% and 57.1 % when nis increased to 2 and 4, respectively. It is recommended that for most absorption studies the linear trapezoidal method be used for prepeak and plateau plasma data and the logarithmic trapezoidal method for postpeak plasma data.

Key words

trapezoidal rule area under the curve pharmacokinetics clearance bioavailability integration method sulfisoxazole 

Copyright information

© Plenum Publishing Corporation 1978

Authors and Affiliations

  • Win L. Chiou
    • 1
  1. 1.Clinical Pharmacokinetics Laboratory and Department of Pharmacy, College of PharmacyUniversity of Illinois at the Medical CenterChicago