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Renal excretion of intravenously infused amoxycillin and ampicillin.

The aim of this study was to determine whether concentration-dependent renal clearance of ampicillin and amoxycillin occurs. The drugs were given as single 20 min i.v. infusions in doses ranging from 1.9 to 2.8 g to nine healthy volunteers using a cross-over design. Plasma and urinary concentrations were determined by a selective liquid chromatographic method using frequent sampling up to 10 and 30 h respectively after termination of the infusion. The renal clearance of the drugs was independent of the plasma concentration. The mean (s.d.) renal clearances of ampicillin and amoxycillin were 167 (24) and 157 (20) ml min-1 1.73 m-2 respectively. The net secretion was about 50% of the total renal clearance of both drugs. The plasma concentration and urinary excretion rate versus time curves indicated a polyexponential decline, which could be described by both a biexponential and a triexponential equation. The former proved to be more reliable, especially in the calculation of micro rate constants. There was a tendency to more sustained plasma concentrations after amoxycillin, also illustrated by a significantly lower mean (s.d.) plasma clearance of this drug, viz. 185 (30) ml min-1 1.73 m-2, as compared to ampicillin, 210 (24) ml min-1 1.73 m-2 (P less than 0.04). There were no major differences in the disposition rate constants and the distribution volumes of ampicillin and amoxycillin. The mean (s.d.) plasma half-life was 1.7 (0.3) h for both drugs. The urinary excretion rate indicated a slower terminal disposition rate however, with ampicillin and amoxycillin half-lives of 3.4 (2.0) and 3.9 (1.2) h respectively. The longer half-life in the terminal phase may be due to increased tubular reabsorption at low urinary concentrations. It was not possible to determine in this study whether the half-life was affected by changes in clearance or volume of distribution. The urinary solubility of the drugs was dependent on pH. This could explain the massive macroscopic crystalluria seen in one subject after amoxycillin. Three hours after termination of the infusion, crystals could no longer be found in the sediment. There was no clinical or laboratory evidence of renal damage.