Pharmacokinetics of 480156-S in elderly patients.
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概要
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2 [4-(2-Thiazolyloxy) phenyl] propionic acid (156-S) is a new acidic nonsteroidalanti-inflammatory and analgesic agent. The pharmacokinetics of 156-S in elderlypatients were studied in comparison with those in healthy volunteers. The elderlypatients females, N=6, age: 84.7±2.1yr old, body weight: 29.7±2.0kg, serumconcentration of albumin: 3.3±0.1g/dl, creatinine clearance (CLcr: 61.3±8 .0ml/min ; all data are represented as mean±S. D.) were given 156-S (300mg) orally andblood and urine samples were taken after dosing. The same schedule applied to healthyvolunteers (males, N=6, 28.0±4.6yr old, 66.7±5. kg, 4.3±0.3g/dl, 91.1±14.0ml/min). The pharmacokinetic arameters of 156-S in both groups were calculated bythe one-compartment model. Although C<SUB>max</SUB> and K<SUB>ab</SUB> of 156-S in elderly patients were notdifferent from those in healthy volunteers, T<SUB>max</SUB>, AUC, t<SUB>1/2</SUB> and Vd of 156-S in elderlypatients were shown to be significantly increased.<BR>More than 90% of the dose of 156-S was excreted in urine until 24 hr afteradministration in both groups. The value of CLr (M-I) (renal clearance of M-I, 156-Smajor metabolite) or CL<SUB>r</SUB> (total M) (renal clearance of total 156-S metabolites) obtained was bigger than that of CL<SUB>cr</SUB> in healthy volunteers, indicating that oxidativemetabolites of 156-S were excreted by glomerular filtration and renal tubular secretion.In elderly patients reduced CL<SUB>r</SUB> (M-I) and CL<SUB>r</SUB> (total M) were shown to be 40% ofthose in healthy volunteer and CL<SUB>cr</SUB> were about 60% . These data suggest that bothglomerular filtration and renal tubular secretion in elderly patients are reducedcompared to those in healthy volunteers.<BR>Hepatic clearance of 156-S in elderly patients, CL<SUB>g</SUB> (hepatic glucronidative clearanceof 156-S) and CL<SUB>m</SUB> (hepatic oxidative clearance of 156-S), were 30-40% of those inhealthy volunteers, indicating that hepatic metabolism of 156-S in elderly patient isreduced compared to those in healthy volunteers. Serum albumin binding ratios weresignificantly different between the two groups and serum concentration of albumin inelderly patients was much lower than in healthy volunteers. From these results, when wegive 156-S to elderly patients, we have to consider the adjustment of the dosing intervalrather than the dose of 156-S.
- 一般社団法人 日本臨床薬理学会の論文
著者
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内田 英二
昭和大学医学部第二薬理学
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小口 勝司
昭和大学医学部第一薬理学教室
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安原 一
昭和大学医学部
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島村 健治
塩野義製薬(株)新薬研究所
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尾熊 隆嘉
塩野義製薬(株)新薬研究所
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山田 秀雄
塩野義製薬
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小林 真一
昭和大学医学部
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坂本 浩二
昭和大学医学部第一薬理学
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島村 健治
塩野義製薬研究所
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山田 秀雄
塩野義製薬研究所
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尾熊 隆嘉
塩野義製薬研究所
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