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. 2016 Sep;6(5):468-474.
doi: 10.1016/j.apsb.2016.07.010. Epub 2016 Aug 6.

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

Wenli Liu  1 , Xiaona Wang  1 , Ruilian Chen  1 , Kaixuan Zhang  1 , Yao Li  1 , Yi Li  1 , Duanyun Si  2 , Junbo Gong  1 , Dianshu Yin  3 , Yongli Wang  1 , Zhenping Wei  1 , Mingshi Yang  4
Affiliations

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

Wenli Liu et al. Acta Pharm Sin B. 2016 Sep.

Abstract

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 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 AUC0-24 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 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.

Keywords: Age difference; Crystal form; Nimodipine; Pharmacokinetics; Polymorphic drug.

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Figures

fx1
Graphical abstract
Fig. 1
Figure 1
XRD patterns (A) and DSC thermograms (B) of H-Nim and L-Nim.
Fig. 2
Figure 2
Dissolution profiles of H-Nim and L-Nim in the dissolution medium of SGF. Data are expressed as Mean±SD, n=3. *P<0.05, **P<0.01 compared to H-Nim.
Fig. 3
Figure 3
Mean plasma concentration-time profiles of H-Nim and L-Nim in 2-month-old rats (A) and 9-month-old rats (B). Data are expressed as Mean±SD, n=5.
Fig. 4
Figure 4
The AUC ratios between L-Nim and H-Nim at different time intervals in 2-month-old rats and 9-month-old rats. Data are expressed as Mean±SD, n=5. *P<0.05 compared to 2-month-old rats.
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