Renal excretion of intravenously infused amoxycillin and ampicillin.

Abstract

1 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. 2 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-' 1.73 m-2 respectively. The net secretion was about 50% of the total renal clearance of both drugs. 3 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-' 1.73 m-2 (P < 0.04). 4 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. 5 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.

Pharmacokinetics of amoxycillin and clavulanic acid in haemodialysis patients following intravenous administration of Augmentin.

“…The terminal half-lives of amoxycillin and clavulanic acid in patients with chronic renal failure, 13.6 and 3.05 h, respectively, were considerably longer than those reported for normal subjects. constitutes a greater proportion of total serum clearance than is the case for clavulanic acid, means of 78 and 49%, respectively (Staniforth et al, 1984;Sjovall et al, 1985). These reductions in total serum clearance are consistent with the data reported by Horber et al (1986).…”

Saturable Pharmacokinetics in the Renal Excretion of Drugs

“…(1962; Mudge et al (1962); N-Acetylcysteine conju- Inoue et al (1981); Monks & Lau Smith et al (1945); Wu & Elliott gates (1987); Newton et al (1986); Schef- Barza et al (1975); Bergan (1984); Bumetanide Rennick (1977); Smith & Lau (1983) Eagle & Newman (1947); Kamiya et Cephalosporins Ings et al (1985); Kamiya et al al. (1983);Sjovall et al (1985); Bins (1983); Kirby & Regamey (1973); & Mattie (1988) Tune (1975); Bins & Mattie (1988) Pentopril Rakhit et al (1987) Captopril Drummer et al (1985; Drummer & Phenosulfonphthalein Goldring et al (1936); Ochwadt & Jarrott (1986); Singhvi et al (1982) Pitts ( Kerremans et al (1982Kerremans et al ( ) (1978 Zidovudine Klecker et al (1987) lodipamide Berndt & Mudge (1968); Milton & Odlind (1985) Abbreviations: cAMP = cyclic adenosine monophosphate; cGMP = cyclic guanidine monophosphate.…”

Nonlinearity of amoxicillin absorption kinetics in human

“…Conventional equations were used for all the models [11]. A two-compartment model was fitted to the IV data [12], allowing for the effect of the duration of the infusion. One-compartment models with either first-order or zeroorder absorption were fitted to the individual oral data.…”