Metabolic fate of loxistatin in rat.
1. The urinary and plasma metabolites of 14C-loxistatin, a new thiol protease inhibitor, were studied after oral administration to rats. 2. The major metabolites in urine were identified as loxistatin acid (M-1), a pharmacologically active form, and its hydroxy metabolites (M-4a and M-4b). These metabolites were also shown to be the major metabolites in plasma. 3. The inhibitory activity of the synthetic metabolite, M-4b, on papain was almost the same as that of loxistatin acid.
Fukushima
K
K
Research Center, Taisho Pharmaceutical Co., Ltd, Saitama, Japan.
Arai
M
M
Tamai
M
M
Yokoo
C
C
Murata
M
M
Suwa
T
T
Satoh
T
T
D000284:Administration, Oral; D000818:Animals; D015853:Cysteine Proteinase Inhibitors / Q000008:administration & dosage / Q000737:chemistry / Q000378:metabolism; D007930:Leucine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000737:chemistry / Q000378:metabolism; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D013058:Mass Spectrometry; D010206:Papain / Q000037:antagonists & inhibitors; D011355:Prodrugs / Q000008:administration & dosage / Q000737:chemistry / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains
D015853:Cysteine Proteinase Inhibitors; D011355:Prodrugs; D010206:Papain; D007930:Leucine; C108192:aloxistatin