Pharmacokinetics of parenterally administered amoxycillin

Abstract

Summary Sodium amoxycillin has been administered by rapid intravenous (i.v.) and by intramuscular (i.m.) injection at 250 mg, 500 mg and 1 g doses to seven healthy subjects. 2 and 5 g doses were administered by slow i.v. infusion over 30 min to the same subjects. Dose response proportionality was examined and pharmacokinetic values determined. Following bolus i.v. injection, mean peak serum concentrations ranged from 33·9 mg 1 −1 after the 250 mg dose, to 99·9 mg 1 −1 after 500 mg and 169·9 mg 1 −1 after 1 g. Corresponding percentages of dose excreted unchanged in the urine in 12 hours were 80, 80 and 75 per cent respectively. After the 30 min infusions, mean peak serum concentrations reached 139·3 mg 1 −1 and 404·8 mg 1 −1 , following 2 and 5 g doses. Respective urinary excretion values were 72 and 75 per cent. There was a linear dose response from the 250 mg to 2 g doses for area under the curve (AUC), but slight deviation from linearity at the 5 g dose. Mean values for biological half-life ranged from 1·1 to 1·3 hours over all doses. Serum concentration results for bolus i.v. injection at 250 mg dose in two subjects on this and two previous occasions were compared. Good reproducibility within subjects was found. After i.m. injection, mean peak serum concentrations were 5·21 mg 1 −1 at 250 mg dose, 12·0 mg 1 −1 at 500 mg and 19·8 mg 1 −1 at 1 g. Corresponding 12 hour urinary excretion results were 74, 71 and 74 per cent. Absorption was rapid in all cases, mean peak concentrations occurring between 0·68 and 0·88 hours. Mean half-lives ranged from 1·0 to 1·1 hours, similar to values obtained following i.v. dosage and again indicating rapid absorption. The calculated overall mean absorption half-life was 0·73 hours. Good dose response proportionality was found for peak serum concentrations, and AUC values. Both intravenous and intramuscular injections were well tolerated.