PHARMACOKINETICS OF DICLOXACILLIN IN PATIENTS WITH CYSTIC FIBROSIS

Abstract

The frequent episodes of peribronchial pneumonia seen in patients with cystic fibrosis require antibiotic administration often with anti-staphylococcal agents. Until now the data upon which to base dosage regimens have not been available. Serum dicloxacillin concentrations and urinary excretion rates were measured in 10 patients ranging in age from 9 to 22 years and in 5 normal adult subjects at various times after oral administration of a single dose (6.25 mg/kg) of antibiotic suspension in order to investigate absorption and disposition kinetics. The disease did not appear to cause impaired absorption of the antibiotic since the total urinary recovery of the drug in the patients usually exceeded that of normal subjects. However, the peak plasma levels and areas under the concentration versus time curves of dicloxacillin were much lower and more variable in the patients than in the normal subjects. Less antibiotic is therefore available for therapeutic effect. This was the result of unusually high renal clearances of dicloxacillin (3x normal). It was significant that the dicloxacillin:creatinine clearance ratios (1.55 versus 0.87, respectively) were larger in the patients than in normal subjects. Because of this rapid renal excretion, treatment of cystic fibrosis patients with dicloxacillin warrants use of increased doses. Measurements of the serum concentration of the antibiotic may be needed to assure adequacy of therapy.