TY - JOUR T1 - In children and adolescents, the pharmacodynamics of high-dose busulfan is dependent on the second alkylating agent used in the combined regimen (melphalan or thiotepa). AU - Bouligand,J, AU - Boland,I, AU - Valteau-Couanet,D, AU - Deroussent,A, AU - Kalifa,C, AU - Hartmann,O, AU - Vassal,G, PY - 2003/11/5/pubmed PY - 2004/8/18/medline PY - 2003/11/5/entrez SP - 979 EP - 86 JF - Bone marrow transplantation JO - Bone Marrow Transplant VL - 32 IS - 10 N2 - A strong relationship has been demonstrated between high systemic exposure to busulfan and the occurrence of hepatic veno-occlusive disease (HVOD) after a busulfan-cyclophosphamide regimen (BU CY). We report a prospective study aimed at exploring the pharmacodynamics of high-dose busulfan combined with either melphalan (BU MEL) or thiotepa (BU TTP) followed by autologous stem cell transplantation in children and adolescents with a malignant solid tumor. Busulfan was given orally at a total dose of 600 mg m(-2). In all, 45 patients with a median age of 6.3 years were included in the study: 25 received BU MEL and 20 received BU TTP. The incidence of HVOD was 44% (CI 95% [23-65%]) in the BU MEL group and 25% (CI95% [9-49%]) in the BU TTP group. In the BU TTP group, patients who developed HVOD had a significantly higher AUC 0-6 h after the 13th dose (6201+/-607 h ng ml(-1)) than those who did not (5024+/-978 h ng ml(-1)) (P<0.05). In the BU MEL group, there was no difference in terms of systemic exposure to busulfan between patients who developed HVOD and those who did not. In conclusion, the guidelines established for monitoring BU CY cannot be extrapolated when busulfan is combined with another drug. SN - 0268-3369 UR - https://www.unboundmedicine.com/medline/citation/14595385/In_children_and_adolescents_the_pharmacodynamics_of_high_dose_busulfan_is_dependent_on_the_second_alkylating_agent_used_in_the_combined_regimen__melphalan_or_thiotepa__ DB - PRIME DP - Unbound Medicine ER -