Human intravenous and intramuscular pharmacokinetics of amoxicillin

Amoxicillin was administered at doses of 500 mg and 1000 mg, intravenously and intramuscularly to normal volunteers in a parallel study. Intramuscular amoxicillin was 100% bioavailable at both dose levels. Mean peak serum levels observed for the 500 mg and 1000 mg doses, respectively, were: i.v. (5 min after dosing) 46 and 74 micrograms/ml; i.m. (30 min after dosing) 14 and 21 micrograms/ml. Six hour trough levels ranged between 0.5 and 0.9 micrograms/ml. Between 50% and 60% of the doses were excreted in urine as intact amoxicillin in the 24 h after dosing. Almost 90% of this excretion occurred in the first 3 h after dosing. There was a statistically significant increase in mean clearance, after i.v. dosing, from the 500 mg level (14.8 l/h) to the 1000 mg level (20.7 l/h) implying that amoxicillin pharmacokinetics are non-linear over this range. Since there was very little difference between mean renal clearances at these dose levels (9.2 and 11.7 l/h, respectively) this clearance change might be due to enhancement of non-renal clearance. It would not be expected that this non-linearity would have any therapeutic influence.