A microcomputer program to determine the precision of elimination rate constant and half-life estimates when sampling...

First-order elimination of drugs is often assumed in pharmacokinetics and elimination rate constant is then frequently determined by log-linear regression analysis from plasma concentration measurements. When the time which elapses between the first and the last plasma sample is short compared to the decay half-life, the elimination rate constant may not be determined with satisfactory precision, in particular because of analytical error. Application of basic principles of linear regression analysis allowed us to quantify the theoretical effect of analytical error on the determination of the drug elimination rate constant in that situation. It was highlighted that the precision of that determination could be efficiently improved by measuring samples in replicate, which should be recommended in practice. A user-friendly program was developed which can be used prospectively to optimize sampling strategy, and retrospectively to estimate the precision of parameter estimates. The program works on IBM PC and compatible microcomputers and is available on request.