Renal failure, hemodialysis, and nafcillin kinetics

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Abstract
Nafcillin (N) pharmacokinetics was studied in 27 subjects with and without renal failure (RF) (determined by endogenous creatinine clearance, CCr)' Elimination rate constants (K) were calculated from serial serum levels of N measured from 2 to 12 hr after a single 500-mg intramuscular injection. Only 4 of 9 hemodialysis patients had measurable levels of Nat 24 hr. The K values for the groups with normal renal function, moderate RF, severe RF, and on hemodialysis were 0.477 hr−1, 0.432 hr−1, 0.369 hr−1, and 0.306 hr−1, respectively. The amounts of injected drug excreted in the urine of the normal renal function, moderate RF, and severe RF groups were 26.6 ± 1.7%, 16.1 ± 3.8%, and 2.0 ± 0.9%, respectively; the renal and nonrenal elimination rate constants for these 3 groups were 0.127 hr−1 and 0.350 hr−1, 0.069 hr−1 and 0.363 hr−1, and 0.007 hr−1 and 0.362 hr−1, respectively. Dialysis had no effect on K values; the maximum nafcillin dialysance was 13.7 ml/min, and was positive in only 5 of 12 determinations. Linear regression analysis of K vs CCr resulted in the following relationship: K = 0.347 + 0.001 CCr. The volumes of distribution for the study groups were 1.06 ± 0.1 L/kg (normals), 0.83 ± 0.07 Llkg (moderate RF), 0.70 ± 0.07 L/kg (severe RF), and 0.78 ± 0.06 Llkg (hemodialysis). We conclude that renal failure alters nafcillin pharmacokinetics only slightly and dosage alterations are not necessary in renal failure, with or without hemodialysis.

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