The Pharmacokinetics of Beraprost Sodium Following Single Oral Administration to Subjects With Impaired Kidney Function.
The purpose of the present study was to evaluate the pharmacokinetics of beraprost sodium (BPS) and its active enantiomer, BPS-314d, in Japanese subjects with impaired kidney function. The plasma and urine concentrations of BPS and BPS-314d were measured following the single oral administration of 120 μg of BPS as the sustained-release tablet, TRK-100STP, under fasting conditions to 18 subjects with impaired kidney function (stage 2, 3, and 4 chronic kidney disease [CKD] as categorized by the estimated glomerular filtration rate) and to 6 age-, body weight-, and gender-matched subjects with normal kidney function (stage 1 CKD). The Cmaxvalues (mean ± SD) of BPS in stage 1, 2, 3, and 4 CKD, respectively, were 84.9 ± 22.9, 119.8 ± 36.4, 190.6 ± 137.3, and 240.2 ± 110.5 pg/mL; its AUC0-48hwere 978 ± 226, 1252 ± 427, 1862 ± 964, and 1766 ± 806 pg·h/mL, respectively, and its cumulative urinary excretion rates were 0.704 ± 0.351%, 0.638 ± 0.292%, 0.485 ± 0.294%, and 0.159 ± 0.136%. The Cmaxvalues of BPS-314d were 22.4 ± 6.4, 30.8 ± 8.5, 46.7 ± 30.6, and 54.4 ± 25.2 pg/mL, its AUC0-48hwere 155 ± 56, 226 ± 67, 341 ± 176, and 329 ± 143 pg·h/mL, and its cumulative urinary excretion rates were 0.428 ± 0.242%, 0.349 ± 0.179%, 0.356 ± 0.270%, and 0.096 ± 0.099%, respectively. Adverse events were reported in 2 subjects with stage 2 CKD and 1 subject with stage 4 CKD. The Cmaxand AUC0-48hof BPS and BPS-314d were higher based on the severity of impaired kidney function. No relationship was observed between the incidence of adverse events and the severity, and tolerability was confirmed. We consider that dose adjustment is not necessary, but BPS is more carefully treated in patients with impaired kidney function.
Pharmaceutical Clinical Research Department, Toray Industries, Inc, Tokyo, Japan.
Masahiro
M
Shimamura
Pharmaceutical Clinical Research Department, Toray Industries, Inc, Tokyo, Japan.
Jun
J
Miyakawa
Clinical Data Science & Quality Management Department, Toray Industries, Inc, Tokyo, Japan.
Masaaki
M
Doi
Clinical Data Science & Quality Management Department, Toray Industries, Inc, Tokyo, Japan.
Kiyonobu
K
Okada
Pharmaceutical Clinical Research Department, Toray Industries, Inc, Tokyo, Japan.
Hajimu
H
Kurumatani
Pharmaceutical Clinical Research Department, Toray Industries, Inc, Tokyo, Japan.
Yoshitaka
Y
Mori
Pharmaceutical Research Laboratories, Toray Industries, Inc, Kanagawa, Japan.
Keiyu
K
Oshida
Clinical Pharmacology Global Development, Astellas Pharma Inc, Tokyo, Japan.
Ikumi
I
Nakajo
Clinical Pharmacology Global Development, Astellas Pharma Inc, Tokyo, Japan.
Keishi
K
Oikawa
Analysis & Pharmacokinetics Research Laboratories, Drug Discovery Research, Astellas Pharma Inc, Ibaraki, Japan.
Fumihiko
F
Ushigome
Analysis & Pharmacokinetics Research Laboratories, Drug Discovery Research, Astellas Pharma Inc, Ibaraki, Japan.
Aiji
A
Miyashita
Pharmaceutical Clinical Research Department, Toray Industries, Inc, Tokyo, Japan.
Masanao
M
Isono
Pharmaceutical Clinical Research Department, Toray Industries, Inc, Tokyo, Japan.
Yohei
Y
Miyamoto
D000284:Administration, Oral; D000368:Aged; D003692:Delayed-Action Preparations; D011464:Epoprostenol / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage / Q000493:pharmacokinetics; D011485:Protein Binding / Q000502:physiology; D051437:Renal Insufficiency / Q000097:blood* / Q000188:drug therapy / Q000652:urine*
D003692:Delayed-Action Preparations; D010975:Platelet Aggregation Inhibitors; C048081:beraprost; D011464:Epoprostenol
TRK-100STP; beraprost sodium; chronic kidney disease; impaired kidney function; pharmacokinetics; prostacyclin derivative