[Show abstract][Hide abstract] ABSTRACT: Stiripentol, a new antiepileptic drug inhibiting cytochrome P450-enzymes, suggested some efficacy when combined with carbamazepine in an open trial in refractory partial epilepsy of childhood. Our objective was to test these results in a placebo-controlled trial. To limit the number of patients included, we used an enrichment and withdrawal design. Among the 67 children entered in a 4-month open add-on stiripentol study following a 1-month single-blind placebo baseline, the 32 responders were randomized for 2 months either to continue stiripentol (n = 17) or to withdraw to placebo (n = 15). If seizures increased by at least 50% after randomization compared with baseline, the patients dropped out (primary end point): there were six patients on stiripentol and eight patients on placebo (not significant). However, a decrease in seizure frequency compared with baseline (secondary end point) was greater on stiripentol (-75%) than on placebo (-22%) (P < .025). Twelve patients experienced at least one adverse event on stiripentol (71%) compared with four patients on placebo (27%); none were reported as severe. The combination of stiripentol and carbamazepine proved to reduce seizure frequency in children with refractory partial epilepsy, although it failed to show a significant impact according to the escape criteria selected as the primary end point in the present study, for ethical reasons.
Preview · Article · Jun 2006 · Journal of Child Neurology
[Show abstract][Hide abstract] ABSTRACT: The aim of this paper was to describe the time-course of the sedative effect of rectal chloral hydrate (75 mg/kg) in children undergoing CT scan or MRI. Twenty children (2.13 +/- 1.43 years old) were administered 75 mg/kg chloral hydrate rectally (chloralhydrat-rectiole rectal formulation, Dr Mann-Pharma Lab, Berlin, Germany), before a CT scan or an NMR imaging. Sedation was measured at specific times using a sedation score of 1-6. Patients were continuously monitored for respiratory and heart rate, systolic and diastolic blood pressures, and oxygen saturation. About 82.35 and 94.11% of the patients had a score of sedation > or = 3 within 15 and 30 min, respectively. The mean time to effective sedation (score > or = 3) was of 0.30 +/- 0.14 h (median time, 0.25 h). The mean duration of effective sedation (score > or = 3) was 1.29 +/- 1.05 h (median duration, 0.75 h). A total of 93.1% of the X-ray sections were obtained without artifact and sedation was considered by radiologists to be efficient for 83.3% of the procedures. This sedation procedure appeared efficient and safe during ambulatory CT scan and NMR imaging. The long-term effect of chloral hydrate, however, remains to be evaluated.
No preview · Article · Jul 2004 · Fundamental and Clinical Pharmacology
[Show abstract][Hide abstract] ABSTRACT: To evaluate the safety of fluoroquinolones (FQ) in comparison with other antibiotics in pediatric patients.
A multicenter, observational, comparative cohort study was conducted between 1998 and 2000 in French pediatric departments. Patients who were receiving systemic FQ were included and matched to control patients who were receiving other antibiotics. Antibiotic-associated potential adverse events (PAEs) were recorded prospectively in both groups, and their rates were compared using univariate and multivariate analyses.
Patients were recruited from 73 centers: 276 patients were exposed to FQ, and 249 composed the control group. Among patients who were exposed to FQ, 23% were younger than 2 years, 33% had cystic fibrosis, and PAEs occurred in 52 patients, leading to withdrawal for 11. The odds ratio for PAE in the FQ group was 3.7 (95% confidence interval: 1.9-7.5) and was not significantly modified after adjustment for potential confounders. Musculoskeletal PAEs also occurred more frequently in the FQ group (3.8%) than in controls (0.4%); they were recorded in 10 patients who were receiving standard FQ doses and were of moderate intensity and transient.
The rates of PAEs and musculoskeletal PAEs were higher for the FQ group than the control group. This observation supports the American Academy of Pediatrics statement restricting off-label FQ use in pediatric patients to second-line treatment in a limited number of situations.
[Show abstract][Hide abstract] ABSTRACT: The therapeutic and toxic effects of amikacin are known to depend on its concentration in plasma, but the pharmacokinetics of this drug in neonates, infants, and children and the influences of clinical and biological variables have been only partially assessed. Therapeutic drug monitoring data collected from 155 patients (49 neonates, 77 infants, and 29 children) receiving amikacin were analyzed by a nonparametric population-based approach, the nonparametric maximum-likelihood method. We assessed the effects of gestational and postnatal age, weight, Apgar score, and plasma creatinine and urea concentrations on pharmacokinetic parameters. There is no specific formulation of amikacin for neonates and infants. We therefore used an error model to account for errors due to dilution during preparation of the infusion. The covariates that reduced the variance of clearance from plasma and the volume of distribution by more than 10% were postnatal age (43 and 28%, respectively) and body weight (30.4 and 17.4%, respectively). The expected reduction of clearance was about 10% for the plasma creatinine concentration. The other covariates studied (Apgar scores, plasma urea concentration, gestational age, sex) were found to have little effect. Simulations showed that a smaller percentage of patients had a maximum concentration in plasma/MIC ratio greater than 8 with a regimen of 7.5 mg/kg of body weight twice daily than with a regimen of 15 mg/kg once a day for MICs of 1 to 8 mg/liter.
Full-text · Article · Jun 2002 · Antimicrobial Agents and Chemotherapy
[Show abstract][Hide abstract] ABSTRACT: To compare the antipyretic efficacy of an initial 30-mg/kg acetaminophen loading dose versus a 15-mg/kg maintenance dose.
A double-blind, parallel-group, randomized clinical trial was conducted. A total of 121 febrile (rectal temperature between 39 degrees C and 40 degrees C) but otherwise healthy outpatients who were 4 months to 9 years of age and weighed 4 to 26 kg were assigned randomly to 1 of the dose groups: 15 mg/kg (n = 62) and 30 mg/kg (n = 59).
In an "intention to treat" analysis, the time to obtain a temperature lower than 38.5 degrees C was significantly shorter in the 30-mg/kg than in the 15-mg/kg group (110 +/- 94 minutes vs 139 +/- 113 minutes). The maximum temperature decrease was significantly higher in the 30-mg/kg than in the 15-mg/kg group (2.3 +/- 0.7 degrees C vs 1.7 +/- 0.6 degrees C). Duration of rectal temperature below 38.5 degrees C was significantly longer in the 30-mg/kg than in the 15-mg/kg group (250 +/- 92 minutes vs 185 +/- 121 minutes, respectively). Adverse events were reported in 6 children in the 30-mg/kg group compared with 5 in the 15-mg/kg group (hyperthermia, hypothermia, vomiting). The difference was not statistically significant.
An initial 30-mg/kg acetaminophen loading dose seemed to be more effective in reducing fever than a 15-mg/kg maintenance dose. No difference was observed regarding clinical tolerance. These data suggest that acetaminophen treatment of fever may be more efficient in an initial loading dose.