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 sodium solution to six healthy subjects in a Latin-Square crossover design. The mean (95% CI) fraction of the dose excreted as unchanged amoxycillin decreased (P < 0.05) from 0.50 (0.44-0.56) after 97 mg amoxycillin sodium (= 0.25 mmol amoxycillin) to 0.23 (0.19-0.27) after 3103 mg (8 mmol), while the mean residence time determined from urinary excretion 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-linearity above 776 mg doses. Michaelis-Menten parameters describing this relationship with respect to amount absorbed were 3.02 mmol for maximum amount absorbed and 1.93 mmol for amount absorbed at half maximum for 0-30 min. These results support a saturable absorption mechanism for amoxycillin which has clinical implications for high oral amoxycillin doses, and for competition with other drugs having capacity-limited absorption.