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

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.

Facile synthesis of PEI-based crystalline templated mesoporous silica with molecular chirality for improved oral delivery of the poorly water-soluble drug

“…The crystalline properties were also evaluated by DSC test, in which the melting point is a standard mean to determine the present of crystals. The characteristic melting peaks of pure NMP were observed at 114.4 °C, which was in accordance with the intrinsic melting point (Fu et al., 2012 ; Liu et al., 2016 ). In contrast, the DSC curves of PEIs@TA-CMS and MCM41 ( Figure 5C,D ) were almost smooth lines, meant the amorphous state of silica materials.…”

“…By loading into the carries, the mesopores effectively restricted NMP in an amorphous state within the channels, which facilitated the drug dissolution. The increased drug dissolution caused by the transformation of the crystalline state could lead to the improvement of absorption after oral dosing (Fu et al., 2012 ; Liu et al., 2016 ). On the other hand, MSNs were carriers with unique structural and textural features.…”

Orally Administered Koumine Persists Longer in the Plasma of Aged Rats Than That of Adult Rats as Assessed by Ultra-Performance Liquid Chromatography-Tandem Mass Spectrometry

“…Limited data are available on the pharmacokinetics of KM in aged rats; however, rodents older than 9 months commonly show signs of the later stages of aging (Liu et al, 2016). For the 1.4 and 7.0 mg•kg −1 orally administered doses, we found that the T max of KM occurred approximately 0.3 h later in aged rats.…”

Comparative Plasma Pharmacokinetics of Ziyuglycoside I from Sanguisorba Officinalis L. between Leukopenia and Normal Rats via UHPLC-MS/MS

“…However, there few literatures have been reported about the pharmacokinetic studies of ZgI during the past 20 years [9]. Recently years, a large number of studies have demonstrated that pharmacokinetics of drugs can be affected by many factors, including age, gender, altitude, drugs and variety of diseases, such as diabetes, Hypertension, estrogen level and so on [10][11][12][13][14][15][16][17]. Actually, drugs are used to treat diseases, and the patients are the ultimate consumers of drugs [18].…”