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Metabolism‐based cyclophosphamide dosing for hematopoietic cell transplant
Author(s) -
McDonald George B.,
McCune Jeannine S.,
Batchelder Ami,
Cole Scott,
Phillips Brian,
Ren Aaron G.,
Vicini Paolo,
Witherspoon Robert,
Kalhorn Thomas F.,
Slattery John T.
Publication year - 2005
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1016/j.clpt.2005.05.005
Subject(s) - cyclophosphamide , pharmacokinetics , dosing , pharmacology , nitrogen mustard , toxicity , medicine , population , confidence interval , area under the curve , chemotherapy , environmental health
When cyclophosphamide (120 mg/kg) is used for hematopoietic cell transplant, the increased area under the curve of carboxyethylphosphoramide mustard (AUC CEPM ) is related to liver toxicity and death. We determined the feasibility of dose‐adjusting cyclophosphamide to a preset metabolic endpoint (AUC CEPM , 325 ± 25 μmol/L · h). In 20 patients blood sampling was done over a 16‐hour period after administration of 45 mg/kg cyclophosphamide; AUC CEPM from 0 to 16 hours was calculated by noncompartmental analysis. The expected AUC CEPM for 0 to 48 hours was estimated, and the second cyclophosphamide dose was determined. The mean second cyclophosphamide dose was 42 mg/kg, and the mean total cyclophosphamide dose was 86 mg/kg (range, 54–120 mg/kg). The mean AUC CEPM for the time from 0 to 48 hours was 296 μmol/L · h (95% confidence interval, 275–317 μmol/L · h). A retrospective analysis indicated that AUC CEPM could be more accurately predicted by use of a population pharmacokinetic model. We conclude that metabolism‐based dosing of cyclophosphamide is feasible and that a lower cyclophosphamide dose does not affect engraftment. Clinical Pharmacology & Therapeutics (2005) 78 , 298–308; doi: 10.1016/j.clpt.2005.05.005