Clinical trials in neonates and children: Report of the pulmonary hypertension academic research consortium pediatric advisory committee.

Drug trials in neonates and children with pulmonary hypertensive vascular disease pose unique but not insurmountable challenges. Childhood is defined by growth and development. Both may influence disease and outcomes of drug trials.

Pediatric cardiovascular safety: challenges in drug and device development and clinical application.

Development of pediatric medications and devices is complicated by differences in pediatric physiology and pathophysiology (both compared with adults and within the pediatric age range), small patient populations, and practical and ethical challenges to designing clinical trials. This article summarizes the discussions that occurred at a Cardiac Safety Research Consortium-sponsored Think Tank convened on December 10, 2010, where members from academia, industry, and regulatory agencies discussed important issues regarding pediatric cardiovascular safety of medications and cardiovascular devices. Pediatric drug and device development may use adult data but often requires additional preclinical and clinical testing to characterize effects on cardiac function and development.

The risks associated with short-term placebo-controlled antihypertensive clinical trials: a descriptive meta-analysis.

Short-term (4-8 weeks) placebo-controlled trials are used to evaluate new antihypertensive drug treatment. To evaluate the consequences of such practice, a descriptive meta-analysis was conducted, consisting of blinded review of original case report forms for all patients who died or left a study before its completion for all short-term, placebo-controlled hypertension trials submitted to the Food and Drug Administration from 1973 through 2001. There were 93 marketing applications or supplements involving 590 individual trials that involved 86137 randomized patients (64438 randomized to experimental drug and 21 699 randomized to placebo) with 12658 patient years of observation.

Distribution of radioactivity and anthracycline-fluorescence in tissues of mice one hour after [14C]-labeled AD 32 administration. Evidence for tissue aglycone formation.

Levels of radioactivity and total anthracycline fluorescence in tissues of A/JAX mice were compared 1 h after IV administration of unlabeled or [14C]-labeled AD 32 (50 mg/kg). Highest levels of both fluorescence and radioactivity were found in the small intestine (including contents) and liver, a result consistent with the known hepatobiliary excretion of AD 32 and metabolites. Significant accumulations of radioactivity and fluorescence were found in kidney, spleen, large intestine (including contents), lung, and heart.

Pharmacologic studies with radiolabeled N-trifluoroacetyladriamycin-14-valerate (AD 32). Comparison of total anthracycline fluorescence and radioactivity in mouse serum and urine.

In connection with pharmacologic studies with AD 32, isotopically-labeled drug prepared from 1-[14C]-trifluoroacetic anhydride and adriamycin-14-valerate was used to determine murine serum and urine levels of radioactivity. Other studies, performed in parallel, measured serum and urinary total fluorescence. Serum fluorescence disappeared in a biphasic pattern, with an initial rapid rate of disappearance followed by a somewhat slower phase.