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The stability of L-phenylalanine mustard in bile
Authors:SY Chang  TL Evans  DS Alberts  IG Sipes
Institution:Section of Hematology and Oncology Departments of Internal Medicine and Pharmacology and the Cancer Center University of Arizona College of Medicine Tucson, Arizona 85724, USA
Abstract:L-phenylalanine mustard (L-PAM) was incubated at 37° C in bile of bovine, canine and human origin. Recovery rate constants of L-PAM from bile were 0.1/hr for canine bile (0–3 hours); 0.18/hr for bovine bile; 0.45/hr for human bile. No significant hydrolysis of L-PAM in canine bile was noted for the period of 3 to 6 hours at 37° C. The incubation of L-PAM in sodium taurocholate solution (1000 molar excess) gave a recovery rate constant 0.15/hr at 37° C. However, the incubation of L-PAM in bilirubin solution (2.5 mg/ml H2O) gave a recovery rate constant of 0.52/hr at 37° C. The high concentration of the parent compound L-PAM seen in vivo in canine bile after i.v. administration may be related to its low in vitro degradation rate in canine bile.
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