Factors affecting the error in the Loo-Riegelman method for estimating the rate of drug absorption. Some suggestions for a practical sampling schedule.

During the development of a new computer program for the Loo-Riegelman method for the estimation of the rate drug absorption, it was found that many factors can affect the accuracy of the estimated absorption rate constant (ka). In this paper a survey of the factors affecting the errors in the estimation of ka by the Loo-Riegelman method is made. By simulating data and computer techniques, the effects of factors related to each step in the calculation procedure as well as the influence of certain pharmacokinetic parameters were studied in detail. If these factors are not well controlled, the estimated error in ka will become very large, in some cases even surpassing 30%. In addition, it was derived that careful attention has to be paid to both sampling time and the number of plasma samples. A "trial and error" method for obtaining an optimal sampling schedule that minimizes the error of ka is presented.