The Use of Gentamicin in Peritoneal Dialysis: I. Pharmacologic Results

The pharmacokinetics of tobramycin and clindamycin were examined in patients undergoing peritoneal dialysis for chronic renal failure. Peak serum levels of tobramycin in functionally anephric patients were less than expected, probably secondary to a larger volume of distribution. Peritoneal dialysis resulted in a significant clearance of tobramycin, with a resultant reduction in serum half-life. The present data suggest that, if bactericidal serum levels of tobramycin are to be maintained in patients undergoing peritoneal dialysis, a parenteral loading dose be administered, followed by either (i) an identical dose every third half-life or (ii) one-half the loading dose every half-life. However, optimal therapy is best achieved by monitoring serum levels to insure appropriate drug dosage. Peak serum levels of clindamycin in functionally anephric patients were approximately twofold greater than those expected in normals after an identical parenteral dose. It is, therefore, recommended that the administered dose of this agent in functionally anephric patients be one-half of that required to produce desired peak serum levels in patients without renal impairment. Peritoneal clearance of clindamycin during dialysis was shown to be essentially zero, indicating that dialysis does not affect clindamycin disposition.

Section: Resultsmentioning

confidence: 96%

Section: Resultsmentioning

confidence: 99%

Effect of Peritoneal Dialysis on Serum Levels of Tobramycin and Clindamycin

Malacoff

Finkelstein

Andriole

1975

“…In 1971, Smithivas et al (10) showed that peritoneal effluent levels of gentamicin after intramuscular administration ranged from 9 to 57% of serum levels in patients undergoing peritoneal dialysis who de- (4) in patients with ascites and bacterial peritonitis revealed peritoneal fluid levels of gentamicin to be 32 to 141% of simultaneously obtained serum levels, but with 5 of the 14 patients studied, peritoneal fluid levels were less than 2 fig/ml. However, interpretation of the therapeutic adequacy of these levels was obscured by the facts that 6 of 14 pairs of simultaneous peritoneal and serum samples were obtained during day 1 of therapy and that all levels were variably obtained from 30 min to 30 h after the last gentamicin dose.…”

Section: Discussionmentioning

confidence: 99%

Peritoneal fluid concentrations of gentamicin in patients with spontaneous bacterial peritonitis

Richey¹,

Schleupner²

1981

Simultaneous peritoneal fluid and serum gentamicin assays were performed at 1- or 4-h intervals after the intravenous administration of gentamicin (3 to 5 mg/kg per day) during nine episodes of spontaneous bacterial peritonitis in cirrhotic patients. Mean peritoneal fluid levels were 4.2 micrograms/ml, whereas simultaneous mean serum levels were 6.1 micrograms/ml (mean percent diffusion into ascites of 67.8%). Three additional patients with uninflamed ascites demonstrated lower levels of diffusion. Regression analysis revealed a positive correlation between simultaneous serum and peritoneal fluid levels. We conclude that diffusion of gentamicin from serum into peritoneal fluid during spontaneous peritonitis is therapeutically adequate if sufficient serum levels are maintained.

“…Weinstein et al (21) found low concentrations of tobramycin in peritoneal dialysate returns in the single patient they studied and suggested that patients with peritonitis may require intraperitoneal instillation of tobramycin in order to achieve therapeutic levels. Low concentrations of gentamicin also have been found in peritoneal dialysates (18). In contrast, the urinary concentrations of tobramycin in the patients undergoing peritoneal dialysis exceeded the minimal inhibitory concentration of the drug for most gram-negative urinary pathogens.…”

Section: Methodsmentioning

confidence: 99%

Pharmacokinetics of Tobramycin in Patients with Stable Renal Impairment, Patients Undergoing Peritoneal Dialysis, and Patients on Chronic Hemodialysis

Jaffé

Meyers

Hirschman

1974

The pharmacokinetics of tobramycin were studied in five patients with stable renal impairment, four patients requiring peritoneal dialysis, and four patients on chronic hemodialysis. The half-life of the drug varied with the level of the serum creatinine in the first group of patients, and the average volume of distribution was 15 liters. Only 49% of the administered dose of tobramycin was recovered during 36 h of peritoneal dialysis. The average clearance of tobramycin during hemodialysis was 49.1 ml/min, and 51.5% of the administered dose was recovered during a 6-h dialysis.