Thiophosphate, alkaline phosphatase

Amifostine (Elhyol) [Antineoplastic/Thiophosphate Cytoprotective] Uses Xerostomia prophylaxis during RT (head, neck, ovarian, NSCLQ -I- renal tox w/ rqjeated cisplatin Action Prodrug, dqjhosphorylated by alkaline phosphatase to active thiol metabohte Dose 910 mg/mVd 15-min IV inf 30 min prior to chemo Caution [C, +/—] CV Dz Disp Inj SE Transient X BP (>60%), NA, flushing w/ hot or cold chills, dizziness, X Ca % somnolence, sneezing Notes Does not -1- effectiveness of cyclophosphamide + cisplatin chemo Interactions T Effects W/ antih5 pertensives EMS Monitor BP for hypotension OD Severe hypotension treat w/IV fluids... 

There are few potent competitive inhibitors for alkaline phosphatase (Table VII) (4, 21, 94, 96, 100, 105-109). Phosphate, thiophosphate, and arsenate have low values for KThese substances are actually substrates and can form a covalent intermediate. However, this is probably not the reason why they are potent inhibitors since in the case of phosphate the Michaelis complex is more stable than the covalent intermediate (30). The values of Kt for phosphate and arsenate at various pH values have been published (SO, 106, 110). 

The organic thiophosphate amifostinc is used to detoxify the reactive metabolites of ci.splatin. e.specially in the kidney. It is dephosphorylated by alkaline pho.sphatase to the active free thiol. This transformation occurs selectively in normal tissues because they have higher alkaline phosphatase activity. higher pH. and better vascularity. 

Thiophosphates (Table 13-7) were subjected to hydrolysis with both add and alkaline phosphatases. Most authors claimed that these compounds are substrates for alkaline phosphatases, but the reaction rate is much lower than with the corresponding phosphates1128, 126L Neumann11291, however, reported that these same S-substituted analogs are resistant to alkaline phosphatases but hydrolyzed by add phosphatases. 

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