Use of a Water-Soluble Busulfan Formulation — Pharmacokinetic Studies in a Canine Model

• Published in: Blood 1995-06, Vol.85 (11), p.3247-3249
• Main Authors: Ehninger, G., Schuler, U., Renner, U., Ehrsam, M., Zeller, K.P., Blanz, J., Storb, R., Deeg, H.J.
• Format: Article
• Language: English
• Subjects: Administration, Oral; Animals; Antineoplastic agents; Biological and medical sciences; Busulfan - administration & dosage; Busulfan - chemistry; Busulfan - pharmacokinetics; Busulfan - toxicity; Chemotherapy; Dimethyl Sulfoxide; Dogs; Half-Life; Injections, Intravenous; Medical sciences; Pharmaceutical Vehicles; Pharmacology. Drug treatments; Sodium Chloride; Solubility; Solutions; Tablets; Water
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood.V85.11.3247.bloodjournal85113247

In a canine model we investigated the toxicity and pharmacokinetics of a water soluble busulfan preparation. Busulfan was dissolved in dimethylsulfoxide (DMSO) and administered either orally or intravenously in a single dose of 1 mg/ kg. The application in either preparation was well tolerated. In seven dogs, peak levels in the range of 730 ng/mL to 1,000 ng/mL were measured after intravenous injection with an area under curve (AUC) of 75 ng · h/kg · mL to 146 ng · h/ kg · mL. It was of note that even the oral administration of the same busulfan preparation resulted in AUC values in the same range as observed after parenteral application. The absorption rate of busulfan tablets in our model was as unpredictable as documented in clinical trials. On the basis of the present study, clinical trials using busulfan dissolved in DMSO given either intravenously or orally appear warranted. This approach should lead to predictable blood levels, reduced toxicity, and increased efficacy of busulfan-containing regimens.