Effect of age on the pharmacokinetics of polymorphic nimodipine in rats after oral administration

The previous investigation has proved that their existed pharmacokinetic difference between the different crystal forms of the polymorphic drugs after oral administration.However,no systemic investigations have been made on the change of this pharmacokinetic difference,resulted either from the physiological or from the pathological factors.In this paper,we used polymorphic nimodipine(Nim) as a model drug and investigated the effect of age difference(2- and 9-month old) on the pharmacokinetics after oral delivery in rats.As the results shown,for L-form of Nim(L-Nim),the AUC0–24 hin 2-month-old rats was 343.68747.15 ng h/m L,which is 23.36% higher than that in 9-month-old rats.For H-form of Nim(H-Nim),the AUC0–24 hin 2-monthold rats was 140.91719.47 ng h/m L,which is 54.64% higher than that in 9-month-old rats.The AUC0–24 h ratio between H-Nim and L-Nim was 2.44 in 2-month-old rats and 3.06 in 9-month-old rats.Since age difference could result in unparallelled change of the absorption and bioavailability of the polymorphic drugs,the results in this experiment are of value for further investigation of crystal form selection in clinical trials and rational clinical application of the polymorphic drugs.

The previous investigation has proved that their existed pharmacokinetic difference between the different crystal forms of the polymorphic drags after oral administration. However, no systemic investigations have been made on the change of this pharmacokinetic difference, resulted either from the physiological or from the pathological factors. hi this paper, we used polymorphic nimodipine (Nim) as a model drug and investigated the effect of age difference (2- and 9-month old) on the pharmacokinetics after oral delivery in rats. As the results shown, for Inform of Nim (L-Nim), the AUC(0-24) h in 2-month-old rats was 343.68+/-47.15 ng . h/mL, which is 23.36% higher than that in 9-month-old rats. For H-form of Nim (H-Nim), the AUC(0-24) h in 2-month old rats was 140.91+/-19.47 ng . h/mL, which is 54.64% higher than that in 9-month-old rats. The AUC(0-24) h ratio between H-Nim and L-Nim was 2.44 in 2-month-old rats and 3.06 in 9-month-old rats. Since age difference could result in unparallelled change of the absorption and bioavailability of the polymorphic drags, the results in this experiment are of value for further investigation of crystal form selection in clinical trials and rational clinical application of the polymorphic drugs. (C) 2016 Chinese Pharmaceutical Association and Institute of Materia Medica, Chinese Academy of Medical Sciences. Production and hosting by Elsevier B.V.