Pupil size , alertness and oxygen saturation did not change over time when loperamide alone or loperamide plus HM30181 was administered while HM30181 significantly increased the systemic exposure to loperamide , i.e. the geometric mean ratio ( 90 % confidence interval ) of AUC ( 0 , tlast ) for loperamide with and without HM30181 was 1.48 ( 1.08 , 2.02 ) .