摘要
目的 :测定大鼠血清及组织中阿霉素的血药浓度 ,研究大鼠静脉给药后脂质体阿霉素 ( L-DOX)与游离阿霉素 ( F-DOX)药代动力学规律及组织分布特征 (靶向定位特征 )。方法 :采用 RP-HPLC法测定阿霉素浓度。色谱柱 :Nova-Pak○R,C1 8( 4 μm,1 5 0 mm× 3.9mm) ,流动相 :甲醇 -乙腈 -0 .0 1 mol/ L磷酸二氢氨 -冰醋酸 ( 5 0∶ 2 0∶ 2 8∶ 0 .6 ) ;流速 :1 .0 ml· min- 1 ;检测波长 :激发波长为 4 79nm,发射波长为 5 87nm,柱温 :30℃。结果 :L-DOX和 F-DOX药代动力学行为符合三房室模型。 L-DOX的半衰期是 F-DOX的 3倍 ,L-DOX药时曲线下面积( AUC)是 F-DOX的 93倍 ;L-DOX在心、肾、胃肠的浓度低于 F-DOX,尤以心内药物浓度明显降低。结论 :L-DOX明显改变
AIM The purpose is to determine the concentration of doxorubicin in rats serum and tissue and study the pharmacokinetics and tissue distribution of free doxorubicin (F DOX)and liposomal doxorubicin ( L DOX)in Sprague Dawley rats following a 6 mg·kg -1 iv. Dose. METHODS Reversed phase HPLC was used. Mobile phase: methanol acetonitrile 0.01 mol·L -1 ammonium dihydrogen phosphate acetic anhydride(50∶20∶28∶0.6);flow rate: 1.0 ml·min -1 ; chromatographic column: Nova Pak(r) C18(4 μm,150 mm×3.9 mm); wavelength: EM: 479 nm,EX: 587 nm; column temperature: 30℃. RESULTS The concentration time curves of free doxorubicin and liposomal doxorubicin were fitted to a three compartment model. The terminal half life of L DOX was 3 flod higher than F DOX. The area under the serum concentration curve (AUC) of L DOX was 93 fold higher than F DOX. The tissue concentration of L DOX in heart, kidney, stomach and intestine, especially in heart, was lower than those of F DOX. CONCLSION Our present studies demonstrate that, compared to F DOX, L DOX significantly alters its pharmacokinetics in serum and tissues targeting.
出处
《中国药科大学学报》
CAS
CSCD
北大核心
2001年第5期354-358,共5页
Journal of China Pharmaceutical University
基金
江苏科委社会发展基金课题 ( 97-BS-78)
