Pharmacokinetics of amrubicin and amrubicinol in small cell lung cancer patients
- VernacularTitle:氨柔比星及氨柔比星醇在小细胞肺癌患者的药代动力学
- Author:
Qian ZHAO
1
;
Bo-Ya WANG
;
Ji JIANG
;
Bei HU
Author Information
1. 中国医学科学院
- Keywords:
amrubicin;
amrubicinol;
pharmacokinetic;
small cell lung cancer
- From:
The Chinese Journal of Clinical Pharmacology
2014;(5):417-420
- CountryChina
- Language:Chinese
-
Abstract:
Objective To evaluate the pharmacokinetics characters of amrubicin and its active metabolite amrubicinol following single and mul-tiple administrations in Chinese small cell lung cancer patients.Methods This study was designed as a multi -center , open label , single and multiple doses study.Twelve patients with extensive stage small cell lung cancer were given iv as amrubicin hydrochloride 40 mg· m-2 for 3 days qd and cisplatin 60 mg · m-2 at day 1.Concentration of amrubicin and amrubicinol in plasma , blood and blood cell were analyzed by LC -MS/MS.WinNonlin was used to calculate the pharmacokinetics parameters.Results Following single -and multiple -administration of amrubicin hydrochloride , and multiple-administration of amrubicin hydrochloride ,for amrubicin, eathylene diamine tetra -acetic acid-K3(EDTAK3) anticoagulant plasma:cmax was (3460 ±1273) and (4080 ±1895 ) ng· mL-1 , AUC0-t was (2050 ±408 ) and (2190 ±412 ) h· ng· mL-1;heparin anticoagulant plas-ma:cmax was (3660 ±1382) and (4360 ±2065) ng· mL-1, AUC0-t was (2100 ±363) and (2220 ±404) h· ng· mL-1;whole blood:cmax was (3240 ±1133 ) and (3920 ±1582 ) ng· mL-1 , AUC0-t was (2150 ±465 ) and (2560 ± 853) h· ng· mL-1;blood cell:cmax was (2100 ±544) and (2500 ±796) ng· mL-1,AUC0-t was (2030 ±465) and (2340 ±653) h· ng· mL-1, respectively.For amrubicinol, EDTAK3 anticoagulant plasma: cmaxwas (18.2 ±3.3) and (30.1 ±3.8) ng· mL-1, AUC0-t was (258 ±43) and (992 ±182) h· ng· mL-1; heparin anticoagulant plas-ma:cmax was (17.9 ±3.8) and (30.9 ±5.7) ng· mL-1, AUC0-t was (259 ±51) and (978 ±190) h· ng· mL-1;whole blood:cmax was (50.3 ±12.8 ) and (81.9 ±19.3) ng· mL-1 ,AUC0-t was (723 ±198) and (2610 ±656) h· ng · mL-1;blood cell:cmax was (83.6 ±19.9) and (153.0 ±25.2) ng· mL-1 , AUC0-t was (1290 ±319) and (4400 ± 831) h· ng· mL-1 , respectively.Conclusion Amrubicinol shows an accumulation after multiple administration , which is similar to Japanese by reported;plasma AUC0-24 is also similar to Japanese after single and multiple administrations;cmax of amrubicinol in blood cells are comparable to Japanese patients , but cmax in plasma tends to be lower.
