Pharmacokinetics and toxicity of oral (-)-(S)-bromofosfamide in lung cancer patients.
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.
Kobylińska
K
K
Department of Pharmacology, Pharmaceutical Research Institute, Warsaw, Poland.
Koralewski
P
P
Sobik
B
B
Gasiorek
M
M
Kobylińska
M
M
D000284:Administration, Oral; D000368:Aged; D018906:Antineoplastic Agents, Alkylating / Q000009:adverse effects* / Q000493:pharmacokinetics*; D019540:Area Under Curve; D001772:Blood Cell Count; D001855:Bone Marrow Diseases / Q000139:chemically induced / Q000473:pathology; D002289:Carcinoma, Non-Small-Cell Lung / Q000378:metabolism*; D002851:Chromatography, High Pressure Liquid; D005260:Female; D006207:Half-Life; D006801:Humans; D007069:Ifosfamide / Q000009:adverse effects* / Q000031:analogs & derivatives / Q000493:pharmacokinetics*; D008175:Lung Neoplasms / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D013056:Spectrophotometry, Ultraviolet
D018906:Antineoplastic Agents, Alkylating; C073801:bromofosfamide; D007069:Ifosfamide