Metabolism
Study Type	Effect Studied	Model Used	Result	Reference
In vitro	Metabolism.	HPLC was used to analyze either the influence of pH or human enzymes (either uridine 5'-diphosphoglucuronyl transferase or enzymes derived from pooled human microsomes or pooled human plasma) on the chemical degradation of kahalalide F.	Kahalalide F was not degraded by the human-derived enzymes. It was also stable at acid pH but under basic and neutral conditions, it was metabolized to kahalalide G.	506275
In vivo	Pharmacokinetics.	Kahalalide F (280 µg/kg) was administered to mice either intravenously or intraperitoneally.	In the intravenous study, plasma levels declined from a peak concentration of 1.0 µM with a t1/2 value of 35 min and there was no accumulation of the drug after repeated administration at 24 h intervals. Total body clearance was 3.8 ml/min/kg and apparent volume of distribution was 199 ml/kg. In the intraperitoneal study, the peak concentration was 0.3 µM approximately 1 h after dosing.	506281
In vivo	Pharmacokinetics.	A phase I study in 33 patients with advanced androgen refractory prostate cancer. Kahalalide F was administered as a daily 1-h intravenous infusion for 5 days every 3 weeks at doses ranging from 20 to 930 µg/m2.	AUC increased in a dose-proportional manner over a dose range of 20 to 560 µg/m2/day. On day 1, total plasma clearance was 11.02 ± 4.54 1/h and the terminal t1/2 of intravenous kahalalide F was 0.54 ± 0.14 h.	543658
In vivo	Pharmacokinetics.	A phase I study in 25 patients in which kahalalide F was administered as a continuous weekly 1-h intravenous infusion at doses ranging from 266 to 1200 µg/m2.	The pharmacokinetic profile was linear over a 266 to 800 (µg/m2/week dose range; at 1200 µg/m2/week, the median t1/2 value was 28 min, median clearance was 74 ml/min.m2 and median AUC was 533.5 ng.h/ml.	470663