Pharmacokinetic and pharmacodynamic studies following oral administration of erythropoietin mucoadhesive tablets to beagle dogs
| Autor: | Yukako Ito, Jun-Ichiro Yoshimitsu, Kanji Takada, Y Ohashi, Nobuhito Shibata, Natarajan Venkatesan, Nobuyuki Sugioka |
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| Rok vydání: | 2005 |
| Předmět: |
Male
Chemistry Pharmaceutical Pharmaceutical Science Administration Oral Absorption (skin) Pharmacology Beagle Intestinal absorption Dosage form Glycerides Rats Sprague-Dawley Dogs Pharmacokinetics Reticulocyte Count Oral administration Medicine Animals Organic Chemicals Erythropoietin Mucous Membrane Dose-Response Relationship Drug business.industry Adhesiveness Rats Acrylates Intestinal Absorption Pharmacodynamics Tablets Enteric-Coated business medicine.drug |
| Zdroj: | International journal of pharmaceutics. 310(1-2) |
| ISSN: | 0378-5173 |
| Popis: | Oral administration of mucoadhesive tablets containing erythropoietin (EPO) and an absorption enhancer Labrasol was studied in rats and dogs. Mucoadhesive tablets were prepared using Sylysia 550 holding the absorption enhancer and Carbopol 974P as a mucoadhesive agent. Mucoadhesive tablets were covered with a water-insoluble backing layer made of cellulose acetate and a pH-sensitive covering layer made of Eudragit L/Eudragit S. Tablet was administered into the rat jejunum at EPO dose of 100 IU/kg and serum samples were collected for 6h. Serum EPO level was analysed with a standard ELISA procedure. After administration, rats showed a maximum serum EPO level of C(max) 70.6 +/- 8.9 mIU/ml. Oral administration of a single tablet containing 100 IU/kg EPO to beagle dogs showed a C(max) of 24.6 +/- 4.1. When EPO dose was increased to 500 IU/kg and the number of tablets was also increased to 5, the C(max) was 54.8 +/- 9.0 mIU/ml. However, when EPO, 100 IU/kg dose was divided into five tablets, the C(max) was 15.5 +/- 1.8 mIU/ml. In the absence of absorption enhancer, the C(max) was 35.8 +/- 3.8 with 500 IU/kg dose distributed among five tablets. Pharmacodynamic studies were carried out following oral administration of mucoadhesive tablets for 6 consecutive days at an EPO dose of 500 IU/kg. Whole blood samples were collected and percent circulating reticulocytes were counted using Miller technique. The increase in percent circulating reticulocytes was found to be 1.7% on day 8 following oral administration. As a control study, EPO was administered by i.v. route at a dose of 300 IU/kg for 3 consecutive days and the percent circulating reticulocytes were counted. Mucoadhesive tablets showed promising results as an oral drug delivery system for protein therapeutics. |
| Databáze: | OpenAIRE |
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