RESUMEN
OBJECTIVE: The effects of age and gender on the single-dose pharmacokinetics of dexloxiglumide, a selective cholecystokinin (CCK1-subtype) receptor antagonist, were assessed in healthy young and elderly male and female subjects. METHODS: In total, 24 males and 24 females (12 young and 12 elderly subjects per gender group) received a single oral dose of 200 mg dexloxiglumide under fasted conditions. Mean (range) ages were 23.8 (18 - 32) and 71.3 (66 - 88) years for young and elderly subjects, respectively. Analysis of covariance (ANCOVA) with age group and gender as factors and body weight as a covariate was performed on the dexloxiglumide pharmacokinetic parameters of peak plasma concentration (C(max)) and the area under the plasma concentration-time curve (AUC). The p values obtained from ANCOVA were considered for the assessment of age and gender effects. RESULTS: A small (approximately 18%) but statistically significant (p < or = 0.036) increase in the area under the plasma concentration-time curve from 0 to time of last quantifiable concentration (AUC(0-t) and the area under the plasma concentration-time curve from 0 to infinity (AUC(0-infinity)) in elderly compared to young subjects was noted. Given the lack of age effects on the other pharmacokinetic parameters of dexloxiglumide, this limited difference is unlikely to be clinically relevant. Without the adjustment for body weights, female subjects exhibited mean C(max) and AUC values approximately 26% and 36% higher than male subjects; however, these exposure differences did not reach statistical significance (p > 0.05) following ANCOVA analysis with body weight as a covariate. Likewise, there were no statistically significant differences (p > 0.05) observed for any other pharmacokinetic parameters between young and elderly and between male and female groups. CONCLUSIONS: Dose adjustments based on age and gender are not necessary. Dexloxiglumide administration was safe and well tolerated in these subjects.