Determination of dose-dependent absorption of amoxycillin 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 had clinical implications for high oral amoxycillin doses, and for competition with other drugs having capacity-limited absorption.