Bioavailability assessment of a brompheniramine taste-masked pediatric formulation in a juvenile porcine model.

A brompheniramine taste-masked pediatric formulation was developed as part of the National Institutes of Health Pediatric Formulation Initiative to help address low patient compliance caused by the bitter taste of many adult formulations. To confirm that the taste-masked formulation can provide a similar pharmacological effect to the previous marketed adult formulations, a juvenile porcine model was used to screen the model pediatric formulation to compare the bioavailability between the marketed brompheniramine maleate and the taste-masked maleate/tannate formulation. Pigs were dosed orally with both formulations and blood samples were obtained from 0 to 48 h. Plasma samples were prepared and extracted using solid-phase extraction. The mass spectrometer was operated under selected ion monitoring mode. The selected ion monitoring channels were set to m/z 319.1 for brompheniramine and m/z 275.2 for the internal standard chlorpheniramine. Calibration curves were linear over the analytical range 0.2-20 ng/ml (r2 > 0.995) for brompheniramine in plasma. The intra- and inter-day accuracies were between 98.0 and 105% with 5.73% RSD precision. The bioanalytical method was successfully applied to a preclinical bioavailability study. The bioavailability profiles were not significantly different between the two formulations, which demonstrates that taste-masking with tannic acid is a promising approach for formulation modification for pediatric patients.

The eternal triangle: benefit, risk, and cost of therapeutic agents.

Some people can undoubtedly tolerate a first-generation H1-receptor antagonist without sedation or other CNS adverse effects, but others cannot. There is no rapid, reliable way of differentiating these two populations. A history of presence or absence of subjective somnolence from one H1-receptor antagonist is not necessarily reliable and has no consistently useful predictive value for subsequent experience with other H1-receptor antagonists. As H1-receptor antagonists are used primarily to treat non-life-threatening disorders, safety should be a prime consideration in selecting one for use, and is surely as important a concern as efficacy and low cost. If your pilot is not permitted to take these medications before going to work, why should your taxi driver, your child's school bus driver, your dentist, your nurse, or your office assistant, to name a few examples, be allowed to do so? When the broad issue of safety is considered, first-generation H1-receptor antagonists may not be as cost-effective as they appear to be. The inherent benefit of any medication is inextricably linked with the inherent risk. It is incumbent on those promulgating the use of the older H1-receptor antagonists to define these benefits and risk further. Lowering the cost of the second-generation, relatively nonsedating H1-receptor antagonists so they are no longer the most expensive medications used in treatment of allergic rhinitis would also help solve the problem of the eternal triangle as it pertains to therapeutic use of H1-receptor antagonists.