Pharmacokinetics of recombinant human soluble thrombomodulin, thrombomodulin alfa in the rat.
1. The study aimed to investigate the pharmacokinetics of thrombomodulin alpha (TM-alpha), human-soluble thrombomodulin in rats. 2. Intravenously administered TM-alpha was eliminated in two phases (T(1/2 alpha) = 0.2-0.3 h and T(1/2 beta) = 6-8 h), and the elimination curve was linear in a dose range of 10-250 microg kg(-1). Based on the results of tissue concentration studies after reaching the steady-state, the highest concentration of TM-alpha was seen in the plasma, suggesting the low levels of transfer to tissues (< or = 22% of plasma levels). 3. In vivo metabolism of TM-alpha was also analysed using high-performance liquid chromatography. The main peak observed in the plasma was TM-alpha, and even 72 h after the last dose of repeated administrations, 80% or more was unchanged form. Approximately half of the radioactivity excreted in the urine was recovered as a peak corresponding to TM-alpha. 4. The results reveal that although plasma clearance was lower in the renally impaired rats, the decrease was not large, with a difference of only about 20%. As a result, although the cause remains unclear, it is considered unlikely that the plasma concentrations of TM-alpha will vary considerably in patients with renal impairment.
Tsuruta
K
K
Pharmaceuticals Research Center, Asahikasei Pharma Co., Shizuoka, Japan. tsuruta.kb@om.asahi-kasei.co.jp
Kodama
T
T
Serada
M
M
Hori
K
K
Inaba
A
A
Miyake
T
T
Kohira
T
T
D000818:Animals; D002851:Chromatography, High Pressure Liquid; D006801:Humans; D007275:Injections, Intravenous; D007668:Kidney / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D007674:Kidney Diseases / Q000139:chemically induced / Q000378:metabolism; D008297:Male; D015202:Protein Engineering; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins / Q000097:blood / Q000493:pharmacokinetics* / Q000652:urine; D012995:Solubility; D018180:Thrombomodulin / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*
D011994:Recombinant Proteins; D018180:Thrombomodulin