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Exposure equivalence between IV (0.8 mg/kg) and oral (1 mg/kg) busulfan in adult patients.
- Source :
-
European journal of clinical pharmacology [Eur J Clin Pharmacol] 2009 Sep; Vol. 65 (9), pp. 903-11. Date of Electronic Publication: 2009 May 08. - Publication Year :
- 2009
-
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.<br />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.<br />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.<br />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.
- Subjects :
- Administration, Oral
Adult
Aged
Antineoplastic Agents, Alkylating blood
Area Under Curve
Biological Availability
Busulfan blood
Clinical Trials as Topic
Dose-Response Relationship, Drug
Drug Administration Schedule
Female
Hematopoietic Stem Cell Transplantation
Humans
Infusions, Intravenous
Male
Middle Aged
Retrospective Studies
Antineoplastic Agents, Alkylating administration & dosage
Antineoplastic Agents, Alkylating pharmacokinetics
Busulfan administration & dosage
Busulfan pharmacokinetics
Transplantation Conditioning methods
Subjects
Details
- Language :
- English
- ISSN :
- 1432-1041
- Volume :
- 65
- Issue :
- 9
- Database :
- MEDLINE
- Journal :
- European journal of clinical pharmacology
- Publication Type :
- Academic Journal
- Accession number :
- 19424688
- Full Text :
- https://doi.org/10.1007/s00228-009-0652-5