Pharmacokinetics and toxicity of oral (-)-(S)-bromofosfamide in lung cancer patients.

Abstract

The pharmacokinetics and toxicity of (-)-(S)-bromofosfamide ((2S)-(2-chloroethylamino)-3-(2-bromoethyl)-1,3,2-oxazaphosphorinae 2-oxide, CAS 146452-37-1, CBM-11) were determined in ten patients with non-small cell lung cancer following an oral dose of 1.38 g/m2 B.S.A. (Body Surface Area). The drug was given as a powder in gelatine capsules to fasting patients. Plasma samples were collected during the first 24 h after administration. All samples, after extraction with chloroform, were assayed by a reverse phase HPLC method using UV detection at 200 nm. Orally administered (-)-(S)-bromofosfamide showed relatively fast absorption kinetics. Peak concentration of 47 micrograms/ml was observed after 1 h. The average half-life was about 5 h. Toxicities associated with oral (-)-(S)-bromofosfamide therapy consisted of symptoms regarding the central nervous system, gastrointestinal tract and urinary tract. Neurotoxic symptoms were the most common clinically significant side effects and probably dose limiting.

• Authors: K Kobylińska, P Koralewski, B Sobik, M Gasiorek, M Kobylińska
• Journal: Arzneimittel-Forschung (Arzneimittelforschung) Vol. 51 Issue 7 Pg. 600-3 ( 2001) ISSN: 0004-4172 [Print] Germany
• PMID: 11505793 (Publication Type: Clinical Trial, Journal Article)

Chemical References

• Antineoplastic Agents, Alkylating
• bromofosfamide
• Ifosfamide

Topics

• Administration, Oral
• Aged
• Antineoplastic Agents, Alkylating (adverse effects, pharmacokinetics)
• Area Under Curve
• Blood Cell Count
• Bone Marrow Diseases (chemically induced, pathology)
• Carcinoma, Non-Small-Cell Lung (metabolism)
• Chromatography, High Pressure Liquid
• Female
• Half-Life
• Humans
• Ifosfamide (adverse effects, analogs & derivatives, pharmacokinetics)
• Lung Neoplasms (metabolism)
• Male
• Middle Aged
• Spectrophotometry, Ultraviolet