Sex- and smoke-related differences in gastrointestinal transit of cyclosporin A microemulsion capsules

The aim of this work was to study the effect of the sex and the smoking status on the pharmacokinetics and the bioequivalence assessment of a branded and a generic cyclosporine A microemulsion formulation in soft-gelatin capsule. Sixteen healthy volunteers (eight women and eight men) participated in a CyA bioequivalence study, with nine of the volunteers being smokers. Sandimmun Neoral (brand formulation; Reference) and Sigmasporin Microral (generic formulation; Test) were administered under fasting conditions. Pharmacokinetic parameters were calculated through non compartmental analysis. Bioequivalence was declared based on the 90% confidence intervals (90% CI) for the T/R ratio of the geometric means for each parameter. In vitro determination of the capsules opening time was performed in simulated gastric fluid without enzyme with USP Apparatus 2. The extent of absorption was similar between both products for all subjects or each sex-group. The absorption rate was similar for both products when considering all subjects, whereas a significant difference in the TMAX between the two products was observed for the male subjects only, which relates to its slower capsule opening time observed in vitro (12.4 versus 6.0 min). No differences were observed in women that could relate to their slower gastric emptying. Differences in drug exposure were observed between smokers and non-smokers. Sex- and smoke-related differences in the gastrointestinal transit should be considered when the on-set time would be determinant for the treatment success of a drug.

Información sobre Derechos de Autor

(Por favor lea este aviso antes de abrir los documentos u objetos)

La legislación uruguaya protege el derecho de autor sobre toda creación literaria, científica o artística, tanto en lo que tiene que ver con sus derechos morales, como en lo referente a los derechos patrimoniales con sujeción a lo establecido por el derecho común y las siguientes leyes

(LEY 9.739 DE 17 DE DICIEMBRE DE 1937 SOBRE PROPIEDAD LITERARIA Y ARTISTICA CON LAS MODIFICACIONES INTRODUCIDAS POR LA LEY DE DERECHO DE AUTOR Y DERECHOS CONEXOS No. 17.616 DE 10 DE ENERO DE 2003, LEY 17.805 DE 26 DE AGOSTO DE 2004, LEY 18.046 DE 24 DE OCTUBRE DE 2006 LEY 18.046 DE 24 DE OCTUBRE DE 2006)

ADVERTENCIA - La consulta de este documento queda condicionada a la aceptación de las siguientes condiciones de uso: Este documento es únicamente para usos privados enmarcados en actividades de investigación y docencia. No se autoriza su reproducción con fines de lucro. Esta reserva de derechos afecta tanto los datos del documento como a sus contenidos. En la utilización o cita de partes debe indicarse el nombre de la persona autora.