Pharmacokinetic and pharmacodynamic assessment of oral valganciclovir in the treatment of symptomatic congenital cytomegalovirus disease.

BACKGROUND: Intravenous ganciclovir administered for 6 weeks improves hearing outcomes in infants with symptomatic congenital cytomegalovirus (CMV) disease involving the central nervous system. METHODS: Twenty-four subjects received antiviral therapy for 6 weeks. Serial pharmacokinetic assessments were performed after administration of valganciclovir oral solution and of intravenous ganciclovir. RESULTS: On the basis of a previous pharmacokinetic study of the use of intravenous ganciclovir in this population, a target AUC12 (area under the concentration-time curve over a 12-h period) of 27 mg x h/L was defined. The median dose of oral valganciclovir administered in the present trial was 16 mg/kg, which produced a geometric mean AUC12 of 27.4 mg x h/L. The bioavailability of valganciclovir was 41.1%. Of the 18 subjects who had detectable CMV in whole blood at baseline or during therapy, 11 had <4 log viral DNA copies/mL at baseline, and 7 had > or =4 log viral DNA copies/mL at baseline; subjects who started the study with the higher viral burden experienced greater decreases in viral load but did not clear virus during the 42-day course of therapy. Neutropenia of grade 3 or 4 developed in 38% of subjects. CONCLUSIONS: In neonates with symptomatic congenital CMV disease, valganciclovir oral solution provides plasma concentrations of ganciclovir comparable to those achieved with administration of intravenous ganciclovir. The results of the present study cannot be extrapolated to extemporaneously compounded liquid formulations of valganciclovir.

Classification of acute respiratory disorders of all newborns in a tertiary care center.

OBJECTIVE: To assess the usefulness of current diagnostic criteria in the understanding of neonatal respiratory distress in a tertiary care hospital. METHODS: We prospectively studied 2824 consecutive deliveries to determine the frequency of respiratory disorders of all types. We used definitions based on standard texts, with borderline cases being classified as having the disease in question. RESULTS: Somewhat less than half of all symptomatic infants met textbook criteria for a respiratory diagnosis. Of this subset, the most common diagnosis was respiratory distress syndrome (RDS), followed by transient tachypnea of newborn (TTN), meconium aspiration syndrome (MAS), pneumonia and others. The 323 infants who fit no standard diagnosis all had self-limited conditions similar to TTN. Most (52%) were well in less than 12 hours. Those still symptomatic after 12 hours differed from the definition of TTN by having a clear chest film (38%) and/or by requiring mechanical ventilation (10%). A slight revision of the traditional diagnostic criteria allowed classification of all these cases. CONCLUSION: More than 50% of newborns with acute respiratory symptoms do not fit textbook definitions, even broad definitions which include borderline cases. The concept of TTN should be expanded to include cases with a normal chest film. In addition, we suggest adding the category "transient respiratory insufficiency of the newbom" (TRIN) for babies ventilated briefly but not demonstrably surfactant deficient or infected. This category probably includes infants with many contributing etiologies.