| Previous studies found that different crystal forms of polymorphic drugs may have an effect on the in vivo pharmacokinetic profiles and oral bioavailabilities of polymorphic drugs.Moreover,the physiological and pathological factors could affect the in vivo absorption and elimination of non-polymorphic drugs.Then,whether these factors will affect,and how they would affect the in vivo pharmacokinetics and oral bioavailabilities of the polymorphic drugs? However,there was no work has been done on the investigation of the influence of these factors on the pharmacokinetics of the polymorphic drugs.While the research of this problem has very important meaning to help us to choose the suitable crystal form of the polymorphic drugs in their dosage form design,clinical trial as well as the rational clinical application.Based on the establishment of HPLC for the analysis of drug in the plasma sample,H-form and L-form of nimodipine（H-Nim and L-Nim）were used as model drugs,a dose of 40 mg/kg them in the form of dry powder were given to 2 month-old healthy rats,9 month-old healthy rats,2 month-old diabetic rats and 9 month-old diabetic rats by intragastric administration respectively,to explore the effects of crystal forms,age and diabetes on the in vivo pharmacokinetics and bioavailabilities of nimodipine.According to the resullts,the AUC（0-24h）and Cmax values of L-Nim were 343.68 ±47.15 ng·h/ml and 41.93 ± 6.34 ng/ml,which were both significantly higher than that AUC（0-24h）and Cmax values of H-Nim（140.91 ± 19.47 ng·h/ml and 26.29 ± 5.00 ng/ml）about 2.44-fold and 1.59-fold respectively,whie the CL value of L-Nim（100.47 ±8.40 l/h/kg）showed 2.62-fold lower than that of H-Nim（263.73 ± 57.70 l/h/kg）.These results indicated that the bioavailability in term of AUC（0-24h）of L-Nim showed an increase of 244 % than that of H-Nim.The Cmax of H-Nim and L-Nim in 2month-old healthy rats showed 1.73-fold and 1.28-fold higher than that in 9month-old healthy rats,The AUC（0-24h）of H-Nim and L-Nim in 2 month-old healthy rats showed 1.73-fold and 1.28-fold higher than that in 9 month-old healthy rats.Nevertheless,the CL value of H-Nim and L-Nim were not significantly different between 9 month-old healthy rats and 2 month-old healthy rats.The bioavailabilities in term of AUC（0-24h）of H-Nim and L-Nim in 2 month-old healthy rats showed anincrease of 155 % and 123 % than that in 9 month-old healthy rats,respectively.Significantly higher values of Cmax（1.22-3.40-fold）and AUC（0-24h）（1.16-2.38-fold）,significantly lower CL value of H-Nim and/or L-Nim were noted in 2 and 9month-old diabetic rats when compared to 2 and 9 month-old healthy rats.The bioavailabilities in term of AUC（0-24h）of H-Nim and L-Nim in diabetic rats were significantly higher than that in the healthy ones about 116 % to 238 %.Moreover,the difference in bioavailabilities resulted from the difference in crystal forms of polymorphic nimodipine was found unparallel in ration to different ages and different physical conditions. |
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