title: Determination of dose-dependent absorption of amoxycillin from urinary excretion data in healthy subjects.
abstract: 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.
authors: Department of Pharmacy, University of Queensland, Brisbane, Australia.
authors: S
authors: S
authors: Chulavatnatol
authors: B G
authors: BG
authors: Charles
mesh_terms: D000328:Adult; D000658:Amoxicillin / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000652:urine; D000704:Analysis of Variance; D002851:Chromatography, High Pressure Liquid; D018592:Cross-Over Studies; D004305:Dose-Response Relationship, Drug; D005260:Female; D006207:Half-Life; D006801:Humans; D007408:Intestinal Absorption; D008297:Male
chemical_list: D000658:Amoxicillin