生物学的同等性とバイオアベイラビリティのジャーナル

概要

The Influence of Formula Concentration on the Absorption of Darbepoetin Alfa after Subcutaneous Administration

Tomonori Tayama, Kazuki Kawakami, Hirotaka Takama, Daisuke Nakashima, Hideji Tanaka, Takayuki Tsuji, Tatsuo Yamamoto, Sakuo Hoshi and Tadao Akizawa

Darbepoetin alfa (DA) is a hyperglycosylated analog of recombinant human erythropoietin (rHuEPO) that stim u- lates red blood cell production. The aim of this st udy 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 concentrat ions of DA, 100 μ g/ml as reference concentration, comparing with 10, 30, 200 μ g/ml as test concentration, by the same dosage (60 μ g). The mean values of the pharmacokinetic parameters were similar after subcutaneous administ ra- tion in each study. The 90% confidence intervals fo r log- transformed C max and AUC 0 -t were within the bioequivalence criteria (0.8-1.25) in each study. I n previ- ous studies, the effect in absorption process of in sulin was correlated to the formula concentration, the formul a con- centration of human growth hormone might not affect ed its absorption. The molecular weight is thought to be caus- ally related to these results. The absorption rate of DA is not affected by its formula concentration because D A, which has relatively higher molecular weight (36,000 Da), is primarily absorbed slowly via lymph vessels regardless of its concentration.