Effects of mezlocillin on the pharmacokinetics of oxacillin and dicloxacillin.
The pharmacokinetics of oxacillin and dicloxacillin, with and without the coadministration of mezlocillin, were studied in 16 patients with normal or severely impaired renal function. After a single administration to patients in terminal renal failure a decrease in total oxacillin clearance from 279 to 159 ml/min/1.73 m2 and total dicloxacillin clearance from 249 to 43 ml/min/1.73 m2 was observed. After coadministration of mezlocillin total oxacillin clearance fell by 38% in all patients irrespective of their renal function. This was caused by a reduction in renal and non-renal elimination rather than by a change in the volume of distribution. With the exception of a minor reduction in renal excretion, the pharmacokinetics of dicloxacillin showed no significant changes. In terminal renal failure the oxacillin dose needs to be reduced by half only when combined with mezlocillin. For dicloxacillin, however, the same dosage adjustment is required irrespective of whether administration is single or combined.
D000328:Adult; D000368:Aged; D004009:Dicloxacillin / Q000378:metabolism*; D004347:Drug Interactions; D006801:Humans; D007674:Kidney Diseases / Q000378:metabolism; D007700:Kinetics; D008802:Mezlocillin / Q000494:pharmacology*; D008875:Middle Aged; D008954:Models, Biological; D010068:Oxacillin / Q000378:metabolism*
D004009:Dicloxacillin; D008802:Mezlocillin; D010068:Oxacillin