Dicloxacillin and cloxacillin: Pharmacokinetics in healthy and hemodialysis subjects

Abstract

Differences in the elimination, distribution, and absorption of dicloxacillin and cloxacillin were studied in a group of healthy individuals with the use of a 2-compartment model. In patients on chronic intermittent hemodialysis, only dicloxacillin was investigated and the results were compared with data obtained in earlier studies on cloxacillin and flucloxacillin. In healthy volunteers the bioavailability after oral administration of 2 gm dicloxacillin or 2 gm cloxacillin amounted to 48.8% and 36.9% of the dose, respectively, when calculated from the area under the serum concentration-time curve, and to 74.1% and 48.5%, respectively, when calculated from the urinary excretion. Individual variation in bioavailability after oral administration was slightly lower for docloxacillin than for cloxacillin. The higher serum concentrations of dicloxacillin, as compared with cloxacillin, are also attributable to slower (renal) elimination (T 1/2: 42 and 33 min, respectively). Analysis of serum concentrations after intravenous administration of 1 and 2 gm dicloxacillin to healthy subjects revealed concentration-dependent kinetics with respect ot renal elimination. In hemodialysis patients the elimination rate of dicloxacillin (T 1/2: 129 min) corresponds with the extrarenal elimination rate in healthy subjects. The bioavailability after oral administration of 1 gm in patients is good (75.9% of the dose).

Saturation of the tubular excretion of beta‐lactam antibiotics.

“…The bolus dose was based on the values for the apparent volume of distribution found in the literature (Nightingale et al, 1975;Nauta & Mattie, 1976;Mandell & Sande, 1980 (Diachema A.G., Zurich, Switzerland). This device has two chambers, each with a volume of 1 ml, separated by a membrane which is permeable forparticles smaller than 5000 D and measures 2 cm .…”

“…Since this is an active process it should have a maximal limit. There are indeed indications in the literature that renal clearance decreases with an increase in the plasma concentration of, for instance, benzylpenicillin (Bryner et al, 1948;Pers, 1954), dicloxacillin and cloxacillin (Nauta & Mattie, 1976), piperacillin (Tjandramaga et al, 1978), azlocillin (Bergan & Michalsen, 1979) and mezlocillin (Bergan, 1984).…”

Dicloxacillin Absorption and Elimination in Children

“…Spino et al [14] [10], but their VD exceeds the average value in infants found in this study, and that reported by others [13], In addition to pseudodifferences between studies introduced by bioassays, the pharma cokinetics of dicloxacillin administered in travenously may be dose-dependent. Nauta and Mattie [12] found in adults that the elimination half-life decreased from 43 to 37 min when the intravenous dose was in creased from 1 to 2 g. Thus, the pharmacoki netic results in different studies cannot be compared when varying doses are used.…”

Pharmacokinetics of β-Lactam Antibiotics

“…In patients with renal dysfunction and requiring hemodialysis, apparent serum clearance is about 60% of normal (NAUTA and MATTIE 1976).…”

“…1973). In subjects who also received an intravenous dose, the bioavailability of orally administered dicloxacillin is estimated to be 74% (NAUTA and MATTIE 1976).…”