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.

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 1-l ± 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.

Bioavailability of oral amo.ricillbz preparationsAbsorption of amo,~icillin was measured in healthy volunteers after oral administration of various capsules and suspensions of two brands. Absorption from suspension is faster and more complete than from capsules. There is a large variation in absorption between volunteers.en suspensie h 25o mg/5 ml. Voor intraveneuze toediening werd een gebufferde oplossing (pH = 8,6) van 75 mg/ml gebruikt. Van MateriaalVan preparaat A 4 werden de volgende presentatievormen onderzocht: capsules h 250 mg, 375 mg en 500 mg; suspensies h z25 mg/5 ml, 25 ~ mg/5 ml en 500 mg/5 ml. Van preparaat B s werden onderzocht: capsules h 375 mg ProefopzetHet onderzoek valt uiteen in drie blokken. In het eerste blok werden de drie capsules van merk A toegediend aan drie proefpersonen, volgens een latijns vierkant. In het tweede blok werden alle vier suspensies aan vier proefpersonen toegediend. Ook hier was de opzet een latijns vierkant. In het derde blok werden bij zes proefpersonen in twee latijnse vierkanten de capsules van 375 mg van beide merken en de suspensie van 250 mg/5 ml van merk A vergeleken. Tot slot gaven wij deze zes proefpersonen 375 mg amoxicilline intraveneus. UitvoeringDe orale preparaten werden op de nuchtere maag toegediend. BIoed werd afgenomen vlak v66r toediening, en I/'2, I, I 1/2, 2, 3, 4 en 6 uur na toediening. De intraveneuze toediening geschiedde onmiddellijk na bereiding. Op de dag van intraveneuze toediening werd bloed afgenomen vlak v66r toediening, Io, 20 en 30 minuten, en l, 2, 3 en 4 uur na toediening. Bloed werd na stollen bij kamertemperatuur gecentrifugeerd. Urine werd verzameld van o tot 6 uur en van 6 tot 24 uur na toediening. Serumen urinemonsters werden bij -2o~ bewaard v66r bepaling. Voor zover de bepalingen niet dezelfde dag werden verricht, werden de monsters gedurende enkele dagen bewaard bij -2o~ Hoewel bij deze temperatuur in het verloop van enkele weken amoxicilline niet stabiel is, valt niet te verwachten dat bovenvermelde procedure de concentraties sterk beinvloed heeft. De bepaling geschiedde met een agardiffusie methode (MArnE e.a. t973), met Sarcina lutea ATCC 9341 als testorganisme.