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Adjustment of cephaloridine (Keflodin): dosage according to its pharmacokinetics
Abstract:
The determination of the serum and urine concentrations of cephaloridine permitted calculation of the pharmacokinetic constants of this antibiotic: after administration of a 1-gram intravenous dose in five normal subjects; after administration of a 1-gram intramuscular dose in five normal subjects, five patients with renal impairment and five patients on maintenance hemodialysis. In normal subjects, serum half-life averaged 1.56 h (Ke=0.4445) after intravenous administration and 1.63 h (Ke=0.4254) after intramuscular administration of a 1-gram dose of the antibiotic. The urinary excretion of cephaloridine over the 6 h following its intramuscular administration in normal subjects amounted to 56.4% of the administered dose. The renal clearance of cephaloridine was 194 ml/min. A linear correlation (Ke=0.0670+0.0028 CrCl) was established between overall elimination rate-constant values and the creatinine clearances of the patients under investigation. These data were used to calculate the maintenance and loading doses and intervals adjusted to creatinine clearance values. Accurate dosage regimens adjusted to the renal status of each individual patient were derived from the calculated values.