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The Pharmacokinetics of Beraprost Sodium Following Single Oral Administration to Subjects With Impaired Kidney Function
Author(s) -
Shimamura Masahiro,
Miyakawa Jun,
Doi Masaaki,
Okada Kiyonobu,
Kurumatani Hajimu,
Mori Yoshitaka,
Oshida Keiyu,
Nakajo Ikumi,
Oikawa Keishi,
Ushigome Fumihiko,
Miyashita Aiji,
Isono Masanao,
Miyamoto Yohei
Publication year - 2017
Publication title -
the journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.92
H-Index - 116
eISSN - 1552-4604
pISSN - 0091-2700
DOI - 10.1002/jcph.835
Subject(s) - renal function , pharmacokinetics , medicine , kidney disease , endocrinology , oral administration , urine , kidney , fractional excretion of sodium , excretion , urology , urinary system
Abstract The purpose of the present study was to evaluate the pharmacokinetics of beraprost sodium (BPS) and its active enantiomer, BPS‐314 d , in Japanese subjects with impaired kidney function. The plasma and urine concentrations of BPS and BPS‐314 d 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 C max values (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 AUC 0‐48h were 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 C max values of BPS‐314 d were 22.4 ± 6.4, 30.8 ± 8.5, 46.7 ± 30.6, and 54.4 ± 25.2 pg/mL, its AUC 0‐48h were 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 C max and AUC 0‐48h of BPS and BPS‐314 d 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.