Gentamicin and standard-dose ibuprofen were administered to an adolescent with cystic fibrosis who developed renal failure and severe vestibulotoxicity. A contributing factor was possible suboptimal intravascular volume status. Because of the potential severity of this drug interaction, hydration status and renal and vestibular functions should be closely monitored in patients receiving ibuprofen and intravenous aminoglycosides concomitantly.

No abstract

Anaesthetists recognize that children with Down's syndrome require special management in a number of clinical situations. There is a widespread clinical impression that it is difficult to achieve adequate sedation and that, following cardiac surgery, these children require higher doses of morphine and additional sedative agents compared to patients without Down's syndrome. We conducted a retrospective chart review of 16 Down's syndrome and 16 matched non-Down's syndrome children who underwent cardiac surgery between 1984 and 1991. The average dose of morphine (continuous infusion) administered per hour was higher in the Down's syndrome group than in the non-Down's syndrome group. The difference was not statistically or clinically significant until the third postoperative day. Down's syndrome patients were more likely to still be receiving morphine on Day 3 than non-Down's patients (P < 0.05). The Down's syndrome patients were also more likely to receive additional sedatives and skeletal muscle relaxants.

The activities of hepatic cytochrome P450 (CYP) 1A2, N-acetyltransferase 2 (NAT-2), xanthine oxidase (XO), and CYP2D6 were evaluated in 12 young children (aged 3-8 years) with mild cystic fibrosis (CF) and 12 age-matched healthy control subjects by use of standard caffeine and dextromethorphan phenotyping methods. Subjects were given 4 oz of Coca-Cola (approximately 35 mg caffeine) (The Coca-Cola Company, Atlanta, Ga) and a single 0.5-mg/kg dose of dextromethorphan. Urine was collected for 8 hours after biomarker administration, and enzyme activity was assessed by use of previously validated caffeine and dextromethorphan molar ratios. CYP2D6 genotyping was also performed in 10 of 12 subjects with CF and 11 of 12 control subjects. There were no significant differences in the urinary molar ratios for any of the enzyme systems evaluated. These data suggest that CF does not alter the activities of CYP1A2, NAT-2, XO, and CYP2D6. Altered biotransformation of drugs in this patient population is likely enzyme- and isoform-specific and thus is apparent for only selected compounds that are substrates for enzymes other than CYP1A2, NAT-2, XO, and CYP2D6.