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Pharmacokinetics of methicillin in patients with cystic fibrosis
Abstract:
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.
Insights
Patients with cystic fibrosis (CF) excrete methicillin faster than normal subjects due to rapid renal clearance. This suggests higher methicillin doses may be needed for CF patients to effectively treat infections.
Area of Science:
- Pharmacokinetics
- Nephrology
- Infectious Diseases
Background:
- Cystic Fibrosis (CF) affects multiple organ systems, including renal function.
- Antibiotic disposition can be altered in patients with CF.
- Understanding methicillin pharmacokinetics is crucial for effective infection treatment in CF.
Purpose of the Study:
- To investigate the disposition of methicillin in normal subjects versus patients with CF.
- To compare serum concentrations, excretion rates, and clearance mechanisms of methicillin between the two groups.
- To determine if CF influences methicillin's pharmacokinetic profile.
Main Methods:
- Single intravenous doses of methicillin (15 mg/kg) were administered to both normal subjects and CF patients.
- Serum concentration-time curves were analyzed to determine the area under the curve (AUC).
- Renal clearance, volume of distribution, metabolic clearance, and creatinine clearance were measured and compared.
Main Results:
- CF patients had a lower average AUC (75% of normal subjects), indicating reduced systemic exposure to methicillin.
- Rapid urinary excretion was observed in CF patients, with significantly higher renal clearance rates (425 ml/min/1.73 m2) compared to normal subjects (362 ml/min/1.73 m2).
- No significant differences were found in volumes of distribution, metabolic clearance, or creatinine clearance between the groups.
Conclusions:
- Patients with cystic fibrosis exhibit accelerated renal excretion of methicillin.
- This rapid clearance suggests active tubular secretion of certain penicillins in CF patients.
- Dosage adjustments, potentially requiring larger doses, may be necessary for effective methicillin treatment in CF patients.