COMPARATIVE-STUDY OF 4 DIFFERENT PHARMACOKINETIC COMPUTER-PROGRAMS - CASE-STUDY OF A FACTOR-VIII PREPARATION

Objective: To compare the pharmacokinetic parameters after a single do se of a monoclonally purified factor VIII concentrate in four differen t computer programs for pharmacokinetic analysis. Setting: Haemophilia unit of a tertiary care university hospital. Methods: Ten patients wi th severe haemophilia A were administered a single dose of 30-50 IU kg (-1) body weight. Blood samples were drawn at different times during t he first 48 h after infusion of factor VIII. Plasma factor VIII activi ty was measured by standard one-stage clotting assay and experimental data were analysed using four computer programs: JANA, PKCALC, F8SD an d PCNONLIN. The pharmacokinetic models of analysis employed in the stu dy were both compartmental and non-compartmental. The parameters compa red were half-lives (t(1/2)) and mean residence time (MRT), volumes of distribution (V) and clearance (CL). Values obtained for each pharmac okinetic parameter in each program for the same model were tested for differences with a multiple analysis of variance (MANOVA). Linear corr elation with the equivalent parameters for each program was also perfo rmed. Results: Pharmacokinetic parameters differed depending on the co mputer program used to analyse the same data set. There were differenc es of statistical significance in t(1/2) and V for one-compartment and two-compartment models derived by some of the programs, but none with the non-compartmental one. CL, considered model independent, showed d ifferences between the programs evaluated. Correlations for each param eter generated were in general good (P < 0.05). Conclusion: Pharmacoki netic parameters differed depending on the computer program used to an alyse the same data set. The same patient data used in different compu ter programs will result in significantly different parameter estimati ons, although the non-compartmental approach is less affected by varia tion, and this should be taken into consideration for comparative purp oses, for the development of new preparations and for the implications in patient care and therapy monitoring.