Drug dose prediction with flexible test doses

This article presents the first known practical method to apply one-compartment pharmacokinetic modeling to prediction of doses for drugs from one or more blood-drug concentrations, without requiring approximations or a computer. It should be useful for regulating doses of orally administered CNS drugs whose effects develop over a day or more, e.g., lithium, antidepressants, and anticonvulsants. Pharmacokinetic calculations for sequences of one, two, and three test doses are condensed into graphs that can be rapidly applied for clinical purposes. These graphs account for dose division, blood sampling time, and drug elimination rate; they show that the ratio of the steady-state day-mean drug level to the test-drug blood level is independent of the half-life if the test level is about a day after the last test dose. The calculations show the same value as experimental measurements for the ratio between steady-state serum lithium level and serum lithium level measured after a test dose. A rational strategy for drug-loading doses is discussed.