The Influence of Formula Concentration on the Absorption of
Darbepoetin Alfa after Subcutaneous Administration |
| Tomonori Tayama1*, Kazuki Kawakami1, Hirotaka Takama1, Daisuke Nakashima1, Hideji Tanaka1, Takayuki Tsuji2, Tatsuo Yamamoto3, Sakuo Hoshi4 and Tadao Akizawa5 |
1Development Division, Kyowa Hakko Kirin Company Ltd., 1-6-1 Ohtemachi, Chiyoda-ku, Tokyo, 100-8185, Japan |
21st Department of Internal Medicine, Hamamatsu University School of Medicine,
1-20-1 Handayama, Higashi-ku, Hamamatsu-shi, Shizuoka, 431-3192, Japan |
3Faculty of Health Promotional Sciences, Department of Health and Nutritional Science,
Hamamatsu University. 1230 Miyakoda-cho, Kita-ku, Hamamatsu-shi, shizuoka, 431-2102, Japan |
4Pharmaco-Business Innovation, Graduate School of Pharmaceutical Sciences, Faculty of Pharmaceutical Science,
The University of Tokyo. 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8654, Japan |
5Department of Nephrology, Showa University School of Medicine, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo 142-8666, Japan |
| *Corresponding author: |
Dr. Tomonori Tayama, Development Division,
Kyowa Hakko Kirin Company Ltd., 1-6-1 Ohtemachi, Chiyoda-ku, Tokyo,
100-8185, Japan,
Tel: +81-3-3282-0983,
Fax: +81-3-3282-0335,
E-mail: tomonori.tayama@kyowa-kirin.co.jp |
|
| Received November 10, 2009; Accepted December 21, 2009; Published
December 22, 2009 |
| Citation: Tayama T, Kawakami K, Takama H, Nakashima D, Tanaka H, et al. (2010) The Influence of Formula Concentration on the Absorption of Darbepoetin Alfa after Subcutaneous Administration. J Bioequiv Availab 2: 001-005. doi: 10.4172/jbb.1000021 |
| Copyright:© 2010 Tayama T, et al. This is an open-access article distributed
under the terms of the Creative Commons Attribution License,
which permits unrestricted use, distribution, and reproduction in any
medium, provided the original author and source are credited. |
| Abstract |
Darbepoetin alfa (DA) is a hyperglycosylated analog of
recombinant human erythropoietin (rHuEPO) that stimulates
red blood cell production. The aim of this study is to
investigate the influence of formula concentration on the
absorption of DA after subcutaneous administration. Three
separate studies were performed to assess the
bioequivalence of four different formula concentrations
of DA, 100 μg/ml as reference concentration, comparing
with 10, 30, 200 μg/ml as test concentration, by the same
dosage (60 μg). The mean values of the pharmacokinetic
parameters were similar after subcutaneous administration
in each study. The 90% confidence intervals for logtransformed
Cmax and AUC0-t were within the
bioequivalence criteria (0.8-1.25) in each study. In previous
studies, the effect in absorption process of insulin was
correlated to the formula concentration, the formula concentration
of human growth hormone might not affected
its absorption. The molecular weight is thought to be causally
related to these results. The absorption rate of DA is
not affected by its formula concentration because DA,
which has relatively higher molecular weight (36,000 Da),
is primarily absorbed slowly via lymph vessels regardless
of its concentration. |
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