Saturation of the tubular excretion of beta‐lactam antibiotics.

Abstract

1 The saturability of the tubular excretion of cloxacillin, benzylpenicillin and cephradine was investigated. 2 Volunteers received a continuous infusion of one of the antibiotics at increasing infusion rates in order to maintain constant plasma concentrations at three different levels. Blood and urine samples were taken every 30 min. Sufficient urinary flow was ensured by a saline infusion (500 ml h-').3 Renal clearance of the antibiotic was calculated for the non-protein bound fraction of the drug. 4 Tubular clearance and tubular excretion rate were estimated by using the renal clearance of the antibiotic minus the glomerular filtration rate; the latter was considered to be equal to creatinine clearance. 5 Data were fitted to a Scatchard transformation and, by nonlinear methods, to a Michaelis-Menten equation.6 Parameters of saturability, i.e. EC50 and maximal tubular excretion rate, were established. The values found for EC50 were 7.7, 93.0 and 266 mg 1-1 for cloxacillin, benzylpenicillin and cephradine, respectively. The values calculated for the maximal tubular excretion rate were 1017, 5535 and 4537 mg h-1, respectively.

Impact of Genetic Knockout of PEPT2 on Cefadroxil Pharmacokinetics, Renal Tubular Reabsorption, and Brain Penetration in Mice

“…AUC cefadroxil (0 -120) or AUC inulin (0 -120) is the area under the cefadroxil or inulin plasma concentration-time curve from 0 to 120 min, as determined by the trapezoidal rule. Since cefadroxil undergoes glomerular filtration, tubular secretion (Bins and Mattie, 1988), and tubular reabsorption (Garcia-Carbonell et al, 1993) in kidney, and given the sequential expression of PEPT1 and PEPT2 in the renal proximal tubule (Smith et al, 1998;Shen et al, 1999), the drug's renal clearance can be represented as…”

Transport of beta-lactam antibiotics in kidney brush border membrane. Determinants of their affinity for the oligopeptide/H+ symporter.

“…The kidney has a key role in the elimination of these antibiotics from plasma, since they are almost completely excreted into the urine whether administered orally or intravenously (1,2). The urinary excretion appears to be the result of two processes: glomerular filtration and secretion into the tubular lumen ( 1,3). Although the transepithelial flux of(3-lactam antibiotics has not been studied in detail, the following steps seem to be involved in the latter process.…”

The tubular excretion of benzylpenicillin in patients with cystic fibrosis.

“…The experimental procedure is described in detail elsewhere (Bins & Mattie, 1988). In brief, three steady-state plasma concentrations (low, high and very high) were achieved by a combination of bolus intravenous injection plus 2.5 h i.v.…”

“…Therefore, multiple regression analysis of the tubular clearance was performed according to Scatchard using the results obtained for patients and for healthy volunteers, and using the reciprocal value of the urinary flow as an additional independent variable. For this purpose the observations from our earlier study of healthy volunteers were used (Bins & Mattie, 1988). It was shown that diuresis had no significant influence on clearance.…”

“…Various explanations have been offered including an increased tubular excretion. Since tubular excretion of ,-lactam antibiotics is a saturable process (Bins & Mattie, 1988), characterized by a maximal rate of excretion and the concentration at which half of that maximal rate is reached (ECU5o), a study with benzylpenicillin was performed to establish whether the values of either of these two parameters differed in patients with cystic fibrosis from those found earlier for healthy volunteers (Bins & Mattie, 1988).…”