Add time:08/13/2019         Source:sciencedirect.com

4-Acetamidophenyl 2,2,2-trichloroethyl carbonate (ATC) was prepared in coarse, regular, and fine particle sizes by sieving and grinding. The powders were found to dissolve in water at significantly different rates in a mechanically stirred system. When administered orally in suspensions to mice, the LD50's of the ATC powders were as follows: coarse—3340 mg./Kg.; regular—2461 mg./Kg.; and fine-1796 mg./Kg. The three ATC powders produced significantly different blood plasma concentrations of total acetaminophen in mice during the 0- to 2-hr. period after oral administration. In humans, the blood plasma concentration curves produced by oral administration of coarse and regular ATC were nearly identical. However, both had lower peaks and slower rates of decline than those produced by fine particle ATC or acetaminophen. Forty-eight-hour recovery of acetaminophen from human urine indicated that all the ATC powders were as efficiently absorbed as acetaminophen itself. It was concluded that ATC is a true prodrug of acetaminophen and that the acetaminophen blood plasma concentrations produced by orally administered ATC can be controlled to some degree by controlling its particle size.

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