Levothyroxine Bioequivalence Study and Its Narrow Therapeutic Index: Comparative Bioavailability Results Between Two Formulations Available in Latin America.

INTRODUCTION: The history of levothyroxine has been linked to advances in the treatment of thyroid disease and to date it is the standard therapy for the treatment of hypothyroidism. Bioequivalence studies are the most widely used method to demonstrate interchangeability, although controversy persists regarding the best design for this molecule declared as a narrow therapeutic index product in many countries. This study aimed to evaluate the pharmacokinetic profile of two formulations of levothyroxine to determine bioequivalence between them. METHODS: This two-period, randomized, crossover, blind study was conducted in 80 healthy volunteers, of both sexes, using a single levothyroxine dose of 600 µg with a washout period of 42 days. Blood sampling was performed at - 30 min, - 15 min, and 0 h pre-dose and 30 min, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 16, 24, and 48 h post-dose. RESULTS: A total of 78 subjects successfully completed both periods. There were no serious adverse events during the study and both formulations were well tolerated. Baseline correction of serum levothyroxine concentrations was performed before statistical analysis. The mean maximum plasma concentration of the test product (Levotiroxina MK®) was 57.49 ng/mL while for the reference product it reached 59.32 ng/mL. Importantly, both test and reference formulations reached maximum concentrations in plasma at about the same time. The areas under the pharmacokinetic curves with the test product showed AUC0-t of 1407.1 ng h/mL and the reference product 1394.3 ng h/mL. The bioequivalence statistical analysis showed that the 90% confidence interval (CI90%) of the ratio of test over reference formulation was within the bioequivalence margins of 90-111%. For Cmax, the test/reference ratio was 96.2% with CI90% of 91.6-100.9%, and for AUC0-t the test/reference ratio was 99.9 with CI90% of 93.3-107.0%. CONCLUSIONS: Both formulations have the same pharmacokinetic profile and are bioequivalent in the narrow therapeutic index required by some health authorities.

Síndrome de Tar (trombocitopenia, aplasia radial): presentación de 2 casos / Tar syndrome (thrombocytopenia-radial aplasia): presentation of 2 cases

Se presentan 2 casos de síndrome de TAR (trombocitopenia y aplasia radial uni o bilateral), correspondiente a dos hermanos. El cuadro se caracteriza por trombocitopenia con ausencia de megacariocitos en la médula; leucocitos y aplasia radial uni o bilateral. Pueden asociarse también variadas otras alteraciones esqueléticas. El diagnóstico diferencial se plantea con los síndromes de Holt-Oram y de Aase y con la anemia de Fanconi. El 40% de los casos fallecen durante el primer año de vida debido a hemorragias digestivas o del sistema nervioso central

Desarrollo psicomotor en preescolares de una población rural, según test de Denver / Psychomotor development of preeschool children in a rural population according to Denver test

El Test de Evaluación del Desarrollo Infantil de Denver fue diseñado para proveer, de un modo rápido y simple, información acerca del nivel de desarrollo psicomotor en niños preescolares. Se estudia el nivel de desarrollo de 104 preescolares de una población rural del Area Metropolitana por medio de la aplicación del Test de Denver, evaluando las áreas de motricidad gruesa; motricidad fina, lenguaje y personal social. El área de conducta que presentó menor rendimiento fue el lenguaje y el grupo etario con mayor evidencia de retraso el de cinco años. Se revisan alguna causas de déficit en el desarrollo psicomotor y se analizan los hallazgos encontrados en la muestra estudiada