Brompheniramine and Chlorpheniramine Pharmacokinetics Following Single-Dose Oral Administration in Children Aged 2 to...

Two pediatric studies characterized brompheniramine and chlorpheniramine pharmacokinetics in a total of 72 subjects, aged 2 to 17 years. A single age-/weight-based oral dose, ranging from 1 to 4 mg, was administered with 2 to 6 oz of water at least 2 hours after a light breakfast. Plasma samples were obtained before and for 72 hours after dosing and analyzed using high-pressure liquid chromatography-tandem mass spectrometry. Pharmacokinetic parameters were estimated using noncompartmental methods; relationships with age were assessed using linear regression. Results indicated that for brompheniramine and chlorpheniramine, C_max was similar across age groups, although it tended to occur earlier in the youngest group. AUC was ∼15% to 30% higher in the oldest age group. As expected, CL_o and V_z /F increased with age; however, following allometric scaling, no age-related differences existed. Because the increase with age for both parameters was similar, no age-related differences in t_1/2,z existed (∼15 hours). Overall, the single doses were well tolerated. Sedation was the most common reported AE and appeared to be more prevalent in the 2- to 5-year-old group. Overall, these results indicate that an age/weight dosing nomogram using a 4-fold range of doses achieves similar C_max and AUC.