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Drug Actions Interactions & Reactions

The pharmacokinetics of gentamicin were examined on two occasions using intravenous and intraperitoneal routes in five children undergoing intermittent peritoneal dialysis for chronic renal failure. Serum, urine and dialysis fluid (DF) were assayed microbiologically for gentamicin and the data were subjected to computer analysis using equations evolved for a two-compartment model which considered the bi-directional flux of the drug. Following IV injection of 1 mg/kg of gentamicin, the apparent volume of distribution averaged 23 percent (range, 13 to 36 percent) of body weight (similar to normal), the mean half-life was 21 hr (range, 9-37 hr; normal, 2 hr) and the peritoneal clearance averaged 4.0 ml/min/m (range, 1.2 to 7.0 ml /min /m 2 ) . During peritoneal administration of gentamicin (15 mg/liter of DF, 0.7 liters/m administered in each cycle over 9 to 12 cycles), serum concentrations increased towards extrapolated steady-state levels which averaged 42 percent (range, 25 to 68 percent) of DF concentrations. The mean renal clearance of gentamicin was only 1.6 m l / min/m while total body clearance ranged from 2.3 to 8.0 ml/min/m, mostly occurring by a variable degree of dialysance. Peritoneal clearances and half-lives of gentamicin were similar in each patient following either treatment mode. The appreciable variability in gentamicin pharmacokinetics among adolescent patients with renal insufficiency necessitates dosage adjustments based on measurments of serum concentrations, according to William J. Jusko, et al. in Kidney International 9:430438 (May) 1976. (6 figures, 3 tables, 19 ref.) Reprints: Dr. William J. Jusko, Clinical Pharmacokinetics Laboratory, Millard Fillmore Hospital, 3 Gates Circle, Buffalo, NY 14209. Serum Protein Binding as a Determinant of Warfarin Elimination