Pharmacokinetics of (-)-(S)-bromofosfamide after intravenous and oral administration in mice.
(-)-(S)-Bromofosfamide ((2S)-(2-chloroethylamino)-3-(2-bromoethyl)-1,3,2-oxazaphosphorinane 2-oxide, CAS 146452-37-1, CBM-11) is a new potential anti-cancer drug, currently under investigation. Its pharmacokinetics and bioavailability were studied in female mice following intravenous and oral administration of the dose of 50 mg/kg. The compound was extracted from plasma samples using chloroform and analyzed by high-performance liquid chromatography with UV detection at 200 nm. Orally administered (-)-(S)-bromofosfamide was absorbed quickly, attaining a maximum level of 33.9 micrograms/ml at 5 min, and was eliminated with a half-life (t1/2) of about 0.9 h. The average half-life of intravenously administered (-)-(S)-bromofosfamide was about 0.7 h. The total plasma clearance (CL) and volume of distribution (Vd) were found to be 0.14 l/h and 4.92 l/kg, respectively. The absolute bioavailability of (-)-(S)-bromofosfamide after oral administration was 105%.
Kobylińska
K
K
Department of Pharmacology, Pharmaceutical Research Institute, Warsaw, Poland.
Kobylińska
M
M
Sobik
B
B
D000284:Administration, Oral; D000818:Animals; D018906:Antineoplastic Agents, Alkylating / Q000008:administration & dosage / Q000493:pharmacokinetics*; D019540:Area Under Curve; D001682:Biological Availability; D002851:Chromatography, High Pressure Liquid; D005260:Female; D006207:Half-Life; D007069:Ifosfamide / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000493:pharmacokinetics*; D007275:Injections, Intravenous; D051379:Mice; D013056:Spectrophotometry, Ultraviolet
D018906:Antineoplastic Agents, Alkylating; C073801:bromofosfamide; D007069:Ifosfamide