Abstract
Objective
This study was conducted to retrospectively compare the area under the curve (AUC) and the total clearance of busulfan (Bu) following oral and intravenous (IV) administrations and to determine which intravenous dose generated equivalent exposure to that of the oral form that has been marketed for decades.
Methods
Patient pharmacokinetics were assessed at dose 9 during a conditioning regimen for stem-cell transplantation and included data from 277 patients for oral Bu (71 from fixed-dose studies and 206 from studies with dose adjustment allowed) and 120 patients for IV Bu (fixed dose). AUCs were compared between patients with fixed dose of oral Bu (n = 71, 1 mg/kg) and those of IV Bu (n = 120, 0.8 mg/kg). Total clearances were calculated for all 277 patients with oral Bu and compared to those with IV Bu, with the ratio of IV-to-oral clearance representing the absolute bioavailability of the oral form.
Results
Oral and IV populations differed on disease-type distribution but presented comparable demography parameters. IV Bu dosing was mostly based on the ideal body weight index while actual body weight or adjusted ideal body weight indexes were mostly used for oral. When normalised to comparable indexes, bioequivalent AUCs were achieved between oral and IV populations. Oral Bu bioavailability was about 80% when calculated from the ratio of IV-to-oral total clearances.
Conclusion
This retrospective study carried out on a large set of data showed that similar plasma exposures were achieved with 1.0 mg/kg oral Bu or 0.8 mg/kg IV Bu.
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Acknowledgements
The authors express their thanks and gratefully acknowledge the contribution of Professor John T. Slattery who, while at Clinical Research Division of the Fred Hutchinson Cancer Research Center, kindly provided the PK data of oral busulfan that gave us the opportunity to carry out this study.
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Léger, F., Nguyen, L. & Puozzo, C. Exposure equivalence between IV (0.8 mg/kg) and oral (1 mg/kg) busulfan in adult patients. Eur J Clin Pharmacol 65, 903–911 (2009). https://doi.org/10.1007/s00228-009-0652-5
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DOI: https://doi.org/10.1007/s00228-009-0652-5