DETERMINATION OF DOSE-DEPENDENT ABSORPTION OF AMOXICILLIN FROM URINARY-EXCRETION DATA IN HEALTHY-SUBJECTS

Measurement of unchanged drug in urine was used to study the rate and extent of amoxycillin absorption after administration of amoxycillin s odium solution to six healthy subjects in a Latin-Square crossover des ign. The mean (95% CI) fraction of the dose excreted as unchanged amox ycillin decreased (P < 0.05) from 0.50 (0.44-0.56) after 97 mg amoxyci llin sodium (= 0.25 mmol amoxycillin) to 0.23 (0.19-0.27) after 3103 m g (8 mmol), while the mean residence time determined from urinary excr etion rate data increased (P < 0.05) from 1.54 (1.32-1.76) h to 2.16 ( 2.01-2.41) h. Plots of total urinary excretion and initial (0-30 min) excretion of unchanged drug vs dose indicated significant non-linearit y above 776 mg doses. Michaelis-Menten parameters describing this rela tionship with respect to amount absorbed were 3.02 mmol for maximum am ount absorbed and 1.93 mmol for amount absorbed at half maximum for 0- 30 min. These results support a saturable absorption mechanism for amo xycillin which has clinical implications for high oral amoxycillin dos es, and for competition with other drugs having capacity-limited absor ption.