チミペロン含有水溶性高分子マトリックスからなる経皮吸収型製剤のラットにおける薬理活性

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  • Pharmacological activities of timiperone transdermal dosage forms composed of water-soluble polymer matrix in rats.

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To prevent the emesis associated with anticancer therapy with chemotherapeutic drugs, various investigations have been conducted into transdermal dosage forms containing timiperone, antipsychotics and strong antiemetics. In the present study, we used the water-soluble polymers as a matrix for transdermal dosage forms. Further, we also evaluated the effect of matrix pH on the inhibition action of timiperone on apomorphine-induced stereotyped behavior in an in vivo model in rats, and compared pharmacological activity with these water-soluble matrices to that obtained with a plaster formulation. Inhibition of timiperone on apomorphine-induced stereotyped behavior was used as an index of percutaneous absorption of timiperone. Results showed that pharmacological activity increased with increasing matrix pH. This finding suggests that the percutaneous absorption of timiperone is pH-dependent. At 4 h after the administration of water-soluble polymer matrices, the pharmacological activity of timiperone was closely similar to that at the same time-point after oral administration of the drugs. Further, this activity was maintained for up to about 8 h after administration. These findings suggest that the transdermal dos age form of timiperone prepared from these water-soluble polymers is effective and longer-acting preparations to prevent the emesis associated with anticancer therapy with chemotherapeutic drugs.

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