@article{oai:kanazawa-u.repo.nii.ac.jp:00013422,
 author = {中積, 泰人 and 藤村, 政樹 and 金森, 一紀 and 笠原, 寿郎 and 柴田, 和彦 and 坂東, 琢磨 and 吉田, 喬 and 中村, 忍 and 松田, 保},
 issue = {3},
 journal = {Japanese Journal of Lung Cancer = 肺癌},
 month = {Jun},
 note = {We investigated the protective effect of fosfomycin (FOM) on cisplatin (CDDP) nephrotoxicity and the pharmacokinetics of CDDP. Thirteen patients with lung cancer underwent combined chemotherapy including CDDP (80mg/m<sup>2</sup>). FOM was administered (4-6g/day) for 5 days by i.v. infusion during the 1st and 3rd courses, but not during the 2nd course. Urinary 24-hour excretion of NAG during the 2nd course remarkably increased and reached a peak at 2-4 days after treatment. The urinary NAG level during the 2nd course was significantly higher than during the 1st and 3rd courses at 3 days after treatment. Area under the curve (AUC) of plasma total platinum (Pt) during the 2nd course were significantly higher than during the 1st course, and that during the 3rd course tended to be higher than that during the 1st course. The maximum level of plasma total Pt during the 2nd course tended to be higher than that during the 1st course. There was no difference in the AUC or the maximum level of plasma free Pt among the three courses. The maximum level of plasma Pt bound to proteins during the 2nd course was higher than that during the 1st course. There was a significant correlation between the AUC of plasma total Pt or plasma Pt level bound to proteins and the peak urinary NAG level. In conclusion, FOM protected against CDDP nephrotoxicity. It is suspected that FOM may affect the pharmacokinetics of plasma total Pt and plasma Pt bound to proteins without changing the antitumor activity of CDDP. Cisplatin(CDDP)の腎障害に対するfosfomycin(FOM)の軽減効果とその時のCDDPの血中動態について検討した.対象はCDDP80mg/m^2を投与された肺癌患者13例で,1・3コース目にFOMを1日4-6g,5日間静脈内投与した.2コース目はNAGの24時間尿中排泄量がCDDP投与2日目から4日目をピークとして上昇を示し,3日目で1・3コースコース目と比べて有意に増加した.総platinum(Pt)濃度のarea under the curve(AUC)については2コース目は1コース目より有意に高く,3コース目は1コース目より高い傾向にあり,最高血中濃度は2コース目は1コース目より高い傾向にあった.非蛋白結合型Ptの血中濃度はいずれのコースでも明らかな差異は認めなかった.蛋白結合型Ptの最高血中濃度については2コース目は1コース目より有意に高かった.また,総Ptおよび蛋白結合型PtのAUCは尿中NAGのピークと有意な相関関係を認めた.以上よりFOMはCDDPの腎障害の軽減作用を示した.薬物動態学的検討からはFOMが総Ptおよび蛋白結合型Ptに何らかの影響をもたらすことが示唆されたが,非蛋白結合型Ptに影響はなく抗腫瘍効果に影響を与えないものと考えられた., 金沢大学医薬保健研究域医学系},
 pages = {287--293},
 title = {Cisplatinの腎障害と血中動態におけるFosfomycinの有用性の検討},
 volume = {35},
 year = {1995}
}