Pronounced QT Prolongation During General Anesthesia in a Child with Left Ventricular Noncompaction Cardiomyopathy: A Case Report.

We report the case of an 8-year-old boy with left ventricular noncompaction cardiomyopathy (LVNC) and QT prolongation who experienced further prolongation of the QTc during general anesthesia for extraction of a maxillary mesiodens. Pronounced prolongation of the QTc was observed after induction of general anesthesia with thiamylal and during emergence. No notable fluctuations in blood pressure, heart rate, and estimated continuous cardiac output were observed. We considered it likely that the QT prolongation was triggered by thiamylal and increased sympathetic nervous system activity. During general anesthesia for children with LVNC and QT prolongation, it is necessary to monitor intraoperative hemodynamic fluctuations and prepare for the possible occurrence of arrhythmias.

Prediction of systemic exposure to cyclosporine in Japanese pediatric patients.

The monitoring of the blood concentration at 2 h (C(2)) after the oral administration of a cyclosporine (CsA) microemulsion was reconfirmed to be useful for the prediction of systemic exposure, the area under the blood concentration-time curve from 0 to 4 h (AUC(0-4)), in a group of Japanese patients, consisting of 33 children aged 5-15 years and 19 young adults aged 16-27 years, with a greater correlation for C(2) (r = 0.927) than the trough concentration (r = 0.488). The dose-normalized AUC(0-4) was independent of gender or indications for CsA, while it depended on body size, i.e., the age (P = 0.065) and total body weight (P = 0.026). MDR1 C3435T had a weak, but insignificant effect (P = 0.072); it was about 22-31% lower in the patients with TT(3435). Co-administration of a steroid and further treatment with nifedipine had a more intensive effect (P = 0.018); co-administration resulted in a 51% increase in the dose-normalized AUC(0-4). A strong effect was also observed for the serum total cholesterol level (P = 0.001). Collectively, the discrepancies in the results on MDR1 C3435T among investigators might be due to variability in the age/total body weight, co-administration drugs or serum lipid level.

Effect of micafungin on cytochrome P450 3A4 and multidrug resistance protein 1 activities, and its comparison with azole antifungal drugs.

The effects of micafungin on cytochrome P450 3A4 (CYP3A4) metabolic and multidrug resistance protein 1 (MDR1) transport activities were investigated and compared with those of amphotericin B and four azole antifungal drugs (ketoconazole, itraconazole, fluconazole and miconazole). The effects on the metabolic activity of CYP3A4 were examined by measuring nifedipine oxidase activity in human liver microsomes and the effects on MDR1 transport activity were evaluated using [3H]digoxin in MDR1-overexpressing LLC-GA5-COL150 cells. An inhibitory effect on CYP3A4 activity was found for ketoconazole, itraconazole and miconazole, with 50% inhibitory concentrations of 11.7, 32.6 and 74.2 nM, respectively. Fluconazole and micafungin had only slight inhibitory effects and amphotericin B had no effect. The MDR1-mediated transport of [3H]digoxin was inhibited by ketoconazole and itraconazole, and slightly by miconazole. It is suggested that micafungin and amphotericin B would be unlikely to cause drug-drug interactions by inhibition of CYP3A4 and MDR1. A positive correlation between the inhibitory effects on CYP3A4 and MDR1 activities was observed, and the physicochemical mechanisms involved and impact on clinical treatment should be studied further.