Subject(s)
Diagnostic Errors/legislation & jurisprudence , Diagnostic Errors/statistics & numerical data , Emergency Service, Hospital/statistics & numerical data , Wounds and Injuries/diagnosis , Academic Medical Centers/statistics & numerical data , Accidents/statistics & numerical data , Humans , Jurisprudence , NetherlandsSubject(s)
Expert Testimony/legislation & jurisprudence , Jurisprudence , Diagnostic Errors , Female , Humans , Liability, Legal , Middle Aged , NetherlandsABSTRACT
1. The tubular excretion of benzylpenicillin (BP) was investigated in six volunteers with cystic fibrosis. 2. The volunteers received a continuous infusion of BP 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-1). 3. The renal clearance of BP was calculated for the non-protein bound fraction of the drug. 4. Tubular clearance and tubular excretion rate were estimated from the renal clearance of the antibiotic minus the glomerular filtration rate; the latter was considered to be equal to creatinine clearance. 5. The data were analysed according to a Scatchard plot and values for ECu50 and maximal tubular excretion rate were calculated. The mean value of ECu50 was 89 +/- 24 (mg l-1 +/- s.d.) and that for the maximal tubular excretion rate was 2603 +/- 714 (mg h-1 +/- s.d.). The latter value was significantly less than that found in a previous study of healthy volunteers, but the ECu50 was similar. 6. It is concluded that the tubular excretory capacity for BP is decreased in patients with cystic fibrosis in direct relation to their low body weight.
Subject(s)
Cystic Fibrosis/urine , Penicillin G/urine , Adolescent , Adult , Child , Cystic Fibrosis/physiopathology , Female , Humans , Infusions, Intravenous , Kidney Tubules/metabolism , Male , Penicillin G/blood , Penicillin G/pharmacokineticsABSTRACT
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-1). 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 l-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.
