Nashimoto A, Sasaki J, Akai S, Sato T, Inada S
Dept. of Surgery, Niigata Cancer Center Hospital, Lederle, Japan.
Gan To Kagaku Ryoho. 1989 Dec;16(12):3747-54.
Patients with advanced gastric cancer were treated with methotrexate-5-fluorouracil sequential therapy. In order to rescue of methotrexate toxicity on the normal proliferating tissue, leucovorin was administered orally to outpatients. As the comparative study, we examined plasma kinetics following oral administration of leucovorin (15 mg) in 6 patients with gastric cancer (received subtotal gastrectomy) and 5 normal subjects. In the patients, peak plasma concentrations of d-1-formyltetrahydrofolate and its main metabolite 5-methyltetrahydrofolate were found after 2 hrs. (7.35 X 10(-7) M, 3.09 X 10(-7) M), and in normal controls also both after 2 hrs. (1.01 X 10(-6) M, 4.89 X 10(-7) M). The active folate metabolite persisted for more than 6 hrs. at over 1 X 10(-7) M that could rescue normal tissue from methotrexate toxicity after leucovorin oral administration in the patients received subtotal gastrectomy.
晚期胃癌患者接受了甲氨蝶呤 - 5 - 氟尿嘧啶序贯疗法。为解救甲氨蝶呤对正常增殖组织的毒性,门诊患者口服亚叶酸钙。作为对比研究,我们检测了6例胃癌患者(接受胃大部切除术)和5名正常受试者口服亚叶酸钙(15毫克)后的血浆动力学。在患者中,d - 1 - 甲酰四氢叶酸及其主要代谢产物5 - 甲基四氢叶酸的血浆峰值浓度在2小时后出现(分别为7.35×10⁻⁷M、3.09×10⁻⁷M),正常对照组在2小时后也出现(分别为1.01×10⁻⁶M、4.89×10⁻⁷M)。在接受胃大部切除术的患者中,口服亚叶酸钙后,活性叶酸代谢产物在超过1×10⁻⁷M的浓度下持续超过6小时,这可以使正常组织免受甲氨蝶呤的毒性。