Evaluation of existing limited sampling models for busulfan kinetics in children with beta thalassaemia major undergoing bone marrow transplantation

Busulfan pharmacokinetic parameters are useful in predicting the outcome of allogeneic bone marrow transplantation (BMT). Standard pharmacokinetic mea surements require multiple blood samples. Various limited sampling models ( LSM) have been proposed for reducing the sample number required for these m easurements, essentially for patients with malignant disorders undergoing B MT. This study was undertaken to evaluate the existing LSM for busulfan pha rmacokinetics to find out the most suitable method for patients with thalas saemia major undergoing BMT. Busulfan levels in plasma samples were analyse d by HPLC. The AUC calculated by non-compartmental analysis using the progr am 'TOPFIT' was compared with previously published LSMs. Our seven sample p harmacokinetic data for AUC calculation was compared with the published LSM s. The three sample models suggested by Chattergoon et al and Schuler et al showed significant agreement with AUC TOPFIT (R-2 = 0.98 and 0.94, respect ively) in our clinical context. Other models resulted in significant over o r under representation of observed values (Vassal's model R-2 = 0.61; Chatt ergoon's two sample model R-2 = 0.84; four sample model R-2 = 0.83; Schuler 's two sample model R-2 = 0.79). By these data the three sample LSM propose d by Chattergoon et al and Schuler et al are suitable for calculation of th e AUC in patients with thalassaemia major undergoing BMT conditioned with o ral busulfan.