Pharmacokinetics of methicillin in patients with cystic fibrosis.

The disposition of methicillin in normal subjects and in subjects with cystic 
fibrosis (CF) was studied after administration of single intravenous doses of 
15 mg/kg. The area under the serum concentration vs. time curve 
for CF patients was, on the average, only 75% of that 
found for normal subjects. The low concentrations in serum were caused 
by more rapid urinary excretion of the antibiotic, with rates of 
renal clearance averaging 425 ml/min per 1.73 m2 in the patients 
with CF and 362 ml/min per 1.73 m2 in the normal 
subjects. No differences were found in volumes of distribution and metabolic 
clearance rates of methicillin or in rates of creatinine clearance between 
the two groups of subjects. These data support previous findings with 
dicloxacillin which show that patients with CF exhibit unusually rapid, active 
tubular secretion of certain penicillins that may necessitate use of larger 
doses of these drugs in treatment of infections. 