Abstract • 157

To allow safe and efficient use of busulfan (BU) which present a great interindividual variability especially in children, we initiated a prospective study to monitor BU plasma concentrations during conditioning regimen (CR) before BMT. BU plasma concentrations were determined by liquid chromatography. For each patient pharmacokinetic parameters was estimated by using USCPACK clinical programs, a bayesian method that allows the use of only 2 to 3 blood samples. Target area under the curve per dose (AUC) was about 4 to 6 (µg/l)h. During the CR, 4 doses were given per day during 4 consecutive days. Daily pharmacokinetic studies were performed for each patient, with adaptive control of dosage regimen for the remaining doses. To this day, 16 patients between 16 months and 15 years (mean 5,6 +/- 4,4 years) were included: 5 Hurler, 3 myelodysplasic syndrome, 3 ANLL, 2 ALL, 1 thalassemia, 1 KI-one, 1 Fanconi anaemia. The adaptation could be totally performed for 13 patients. Initial CR were between 16 to 20mg/kg or 600 mg/m2 of BU. The final AUC per dose was in the interval in 9/13, over 6 (µg/l)h in 3/13 patients and under 4 (µg/l)h in one case. We increased dosage regimen in 5 children, decreased it in 8 cases. Mean total clearance during the 4 days was 0.209+/-0.07 (ml/h)kg. Mean elimination half life was 2.47 +/- 1.24 h. Between day 1 and day 2, the clearance was 10 to 50 % (med=35%) decreased for 8 patients, 10 to 50% (med=19%) increased for 4 patients. Because Hurler syndrome is a predominant pathology in our study, we individualized the Hurler results. We had to decrease the previous high-dose regimen in 3 of the 5 patients while the dose was maintained in 2 patients. Mean clearance in this group was 0.227 versus 0.201(ml/h)kg for other pathologies (p=0.4), and mean half life was 2.08 versus 2.64 h (p=0.2). This study showed that standard BU dosage regimens could never be kept unchanged during the 4 days of CR. Generally dosage regimens were slightly increased in hematological malignancies, and decreased in Hurler. We could not find any difference of BU disposition between Hurler syndrome and other pathologies in contrary to previous studies, but these preliminary results have to be confirmed. The great intra and interindividual variation in BU pharmacokinetic confort us in a daily adaptive control of dosage regimens of BU in CR.