title: Evaluation of aminoglycoside disposition in patients previously treated with cisplatin.
abstract: The alterations in aminoglycoside disposition in patients previously treated with cisplatin were determined by reviewing the medical records of 37 cancer patients. The patients received 44 courses of an aminoglycoside antibiotic (gentamicin, n = 27; amikacin, n = 14; and tobramycin, n = 3). The mean (SD) half-life of 171 (120) min was greater than our previously published mean aminoglycoside half-life in children with cancer who were not receiving cisplatin. Twenty-five of 44 courses were completed without an aminoglycoside dosage reduction and only 5 courses were discontinued because of delayed aminoglycoside elimination. There was no significant difference in the duration of aminoglycoside therapy between the group that had a dosage reduction and the group that did not [6.6 (2.3) versus 5.8 (2.9) days, p = 0.42, respectively]. Multiple linear regression analysis of patient variables identified serum creatinine and cumulative cisplatin dose as the best predictors of aminoglycoside half-life (r2 = 46.0%, p less than 0.001). The only predictor of aminoglycoside clearance was serum creatinine (r2 = 35.2%, p less than 0.001). Patients previously treated with cisplatin are at greater risk for delayed aminoglycoside elimination. Prior administration of cisplatin is not an absolute contraindication to the use of aminoglycoside antibiotics. When clinically indicated, patients who have previously received cisplatin and have apparently normal renal function should be treated cautiously with standard doses of aminoglycoside antibiotics, and pharmacokinetic monitoring should be routinely performed.
authors.affiliation: Pharmaceutical Division, St. Jude Children's Research Hospital, Memphis, Tennessee.
authors.forename: M L
authors.initials: ML
authors.lastname: Christensen
authors.forename: C F
authors.initials: CF
authors.lastname: Stewart
authors.forename: W R
authors.initials: WR
authors.lastname: Crom
mesh_terms: D058186:Acute Kidney Injury / Q000139:chemically induced; D000293:Adolescent; D000328:Adult; D000617:Aminoglycosides; D000900:Anti-Bacterial Agents / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics*; D002648:Child; D002675:Child, Preschool; D002945:Cisplatin / Q000009:adverse effects*; D003404:Creatinine / Q000097:blood; D004347:Drug Interactions; D005260:Female; D006207:Half-Life; D006801:Humans; D007223:Infant; D008297:Male; D012189:Retrospective Studies
chemical_list: D000617:Aminoglycosides; D000900:Anti-Bacterial Agents; D003404:Creatinine; D002945:Cisplatin