The pharmacokinetics of irbesartan in hypertensive children and adolescents.

An open-label study was conducted to characterize the pharmacokinetics and antihypertensive response to irbesartan in children (1-12 years) and adolescents (13-16 years) with hypertension. Patients received single once-daily oral doses of irbesartan 2 mg/kg (maximum of 150 mg once daily) for 2 to 4 weeks (+/- nifedipine or hydrochlorothiazide). Plasma irbesartan concentrations were determined by a validated high-performance liquid chromatography/fluorescence method from blood samples taken predose, up to 24 hours after dosing on Day 1, and up to 48 hours after the final dose. The plasma concentration-time profiles were similar between the 6- to 12-year and the 13- to 16-year age groups and to that previously determined from a study of adult subjects receiving approximately 2 mg/kg (i.e., 150 mg) oral irbesartan once daily. Mean reductions in systolic/diastolic blood pressure were 16/10 mmHg at Day 28 with irbesartan monotherapy (n = 8). Irbesartan was well tolerated and may be a treatment option for pediatric hypertensive patients.

Evaluation of empiric vancomycin therapy in children with fever and neutropenia.

A retrospective evaluation was conducted to determine which children admitted for fever and neutropenia required empiric vancomycin therapy, and to develop a clinical pathway for appropriate treatment. Chart review identified 109 admissions of 36 pediatric oncology patients for fever and neutropenia, of which 88 were eligible for analysis. Blood cultures isolated 17 gram-positive organisms; coagulase-negative staphylococci and viridans group streptococci were cultured most frequently (82%). We concluded that previous high-dose cytarabine therapy, inflamed central access site, and hypotension or septic shock are possible indicators of febrile, neutropenic patients at high risk for gram-positive pathogen isolation. These predictors then were used to determine which children would receive empiric vancomycin therapy.

Pemoline therapy resulting in liver transplantation.

OBJECTIVE: To describe a case of pemoline-induced liver failure resulting in liver transplantation. CASE SUMMARY: A 9-year-old white boy, diagnosed with attention deficit/hyperactivity disorder (ADHD) and treated with pemoline, developed signs and symptoms of liver failure. Pemoline therapy was discontinued, but the patient's liver function continued to decline. Ultimately, a liver transplantation was required. DISCUSSION: Pemoline, an agent used in ADHD treatment, has been associated with hepatotoxicity with the majority of cases occurring in pediatric patients. To our knowledge, this is the second reported case of pemoline-induced liver failure resulting in liver transplantation. The mechanism of action remains unclear, with several hypotheses being postulated including hypersensitivity reactions, dose-related phenomena, and autoimmune-mediated reactions. CONCLUSIONS: With increasing evidence linking pemoline to liver failure, this agent should not be considered first-line therapy for ADHD. Prior to initiating therapy, baseline liver function tests should be obtained and closely monitored, and parents and patients should be educated on the signs and symptoms of liver toxicity.