Posted on July 30, 2022
Information on effects of food on the pharmacokinetics of 48 compounds (66.7%) out of the 72 investigated oral antineoplastic drugs was obtained. There were 30 compounds for which dietary conditions were defined in the usages or the precautions described in the package inserts; 15 compounds required postprandial administration, and the other 15 compounds required fasting administration (Table 1). The medians (maximumimum, minimum) of the AUC ratios, Cmax ratios and Tmax ratios were 1.08 (8.96, 0.61), 0.94 (, 0.30) and 1.91 (3.92, 0.50), respectively. There was a positive correlation between ln (AUC ratio) and ln (Cmax ratio) (r 2 = 0.86) (Fig. 1).
Relationship within known restaurants consequences and you can physicochemical properties obtained from the for the silico forecasts
Classification based on the type of the effect of food based on the AUC ratio resulted in 14 compounds in the absorption increase group, 26 compounds in the absorption invariant group, and 7 compounds in the absorption decrease group. Classification based on the Tmax ratio resulted in 15 compounds in the absorption time prolongation group, 23 compounds in the absorption time invariant group, and www.datingranking.net/es/citas-con-perros-es no compounds in the absorption time shortening group. The compounds in the absorption increase group and absorption decrease group are shown in Table 2. The AUC increased by a factor of 8 or more due to food in the cases of bexarotene and abiraterone acetate. On the other hand, AUC decreased by approximately 60% due to food in the cases of capecitabine and afatinib.
In silico anticipate of your physicochemical attributes regarding oral antineoplastic pills
Using JMP® Pro 13.1.0., we analyzed the relationship between the reported effects of food and the physicochemical properties obtained from in silico predictions. The bivariate relationship was analyzed using AUC changes as the objective variables and logP as the explanatory variable. The medians of the logP value (maximum, minimum) were 4.97 (7.46, 1.59) in the AUC increase group, 2.40 (5.44, ? 1.99) in the AUC invariant group, and 4.05 (5.56, 1.28) in the AUC decrease group. The median in the AUC increase group was significantly higher than that of the AUC invariant group (P = 0.0054) (Fig. 2a). In the bivariate analysis of AUC changes and solubility in FaSSIF, the median of lnFaSSIF was ? 4.66 in the AUC increase group, ? 2.28 in the AUC invariant group and ? 3.41 in the AUC decrease group. The median in the AUC increase group was significantly low than that of the AUC invariant group (P = 0.0013) (Fig. 2b). Similarly, in FeSSIF, the median of lnFeSSIF in the AUC increase group was lower than that of the AUC invariant group, although the difference was not significant (Fig. 2c). In the bivariate analysis of the changes in Tmax and solubility in FaSSIF, the median of lnFaSSIF was ? 1.88 in the Tmax prolongation group and ? 4.27 in the Tmax invariant group (Fig. 3). The median in the Tmax prolongation group was significantly higher than that of the Tmax invariant group (P = 0.0129), and a similar trend was observed for FeSSIF. However, no significant difference was observed between the Tmax prolongation group and the Tmax invariant group in the bivariate analysis of the changes in Tmax and logP. As described above, we found that compounds for which the absorption was increased by food had higher logP and lower solubilities in FaSSIF and FeSSIF and that compounds for which the absorption was decreased had higher solubilities in FaSSIF. On the other hand, no relationship between the effects of food and other physicochemical properties, such as the nonionized fraction, were observed.
a Relationship between AUC changes and logP. b Relationship between AUC changes and the solubility in FaSSIF. cRelationship between AUC changes and the solubility in FeSSIF. d Relationship between AUC changes and FaSSIF/FeSSIF solubility ratio. Steel-Dwass test. **:P < 0.01. *:P < 0.05. NS: not significant