New pharmacokinetic methods: I. Estimation of mean serum concentration from trough serum concentration

An equation is derived to estimate mean steady state serum concentration (Css) from trough steady state serum concentration (Cmin) which can be used for drugs with either linear or nonlinear pharmacokinetic properties. In 15 subjects receiving phenytoin monotherapy, estimated Css did not differ significantly from measured Css, while Cmin differed significantly (P less than .0001) from measured Css and estimated Css. Clearance (CL) and elimination half-life (t1/2) values determined by stable isotope tracer methods or by standard equations and measured Css or estimated Css did not differ significantly, while CL and t1/2 values calculated with standard equations and Cmin differed significantly (P less than .02) from values obtained by any of the other three methods. We conclude: 1) Cmin values and CL and t1/2 values calculated with Cmin values may differ significantly from Css values and CL and t1/2 values calculated with Css; 2) accurate estimates of Css and of CL and t1/2 can be obtained using our procedure to correct a Cmin value to an estimated Css value.