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Cefadroxil kinetics in patients with renal insufficiency
Clinical Pharmacology and Therapeutics
|May 1, 1979
Summary
Cefadroxil absorption and urine concentrations remain adequate across varying kidney function. Dosage adjustments may be needed for patients with creatinine clearance (CCr) below 25 ml/min to prevent cefadroxil accumulation.
Area of Science:
- Pharmacokinetics
- Nephrology
- Infectious Diseases
Background:
- Cefadroxil is a widely used cephalosporin antibiotic.
- Renal function significantly impacts drug elimination.
- Understanding cefadroxil's behavior in patients with impaired kidney function is crucial for safe and effective dosing.
Purpose of the Study:
- To investigate the pharmacokinetic parameters and bioavailability of cefadroxil in individuals with varying degrees of renal function.
- To assess the impact of endogenous creatinine clearance (CCr) on cefadroxil's absorption, distribution, and elimination.
- To determine the adequacy of cefadroxil urine concentrations for treating susceptible bacterial infections in renal impairment.
Main Methods:
- Twenty subjects with diverse renal function, including two on hemodialysis, participated in the study.
- Subjects ingested two 500-mg capsules of cefadroxil after an overnight fast.
- Kinetic parameters such as peak serum concentration, absorption rate (ka), distribution volume (Vd ext), and plasma elimination rate were analyzed in relation to CCr.
Main Results:
- Peak serum cefadroxil concentrations varied (12-57 mg/L) and inversely correlated with CCr.
- Oral absorption rate (ka) was unaffected by renal function (0.76 +/- 0.50 hr-1).
- Urinary recovery was substantial (45%-106% within 48 hr for CCr > 8 ml/min), with adequate urine concentrations observed even in severe renal failure (CCr < 10 ml/min).
- Plasma elimination rate was dependent on CCr, with minimal nonrenal drug removal.
- Tubular secretion of cefadroxil was present when CCr exceeded renal clearance, indicating active renal excretion.
Conclusions:
- Cefadroxil exhibits predictable oral absorption regardless of renal function.
- Adequate cefadroxil concentrations are achieved in urine, even in severe renal impairment, suggesting therapeutic potential.
- Little drug accumulation is expected with standard 8- to 12-hour dosing, except in cases of CCr less than 25 ml/min.