| Title | Hepatic Artery and Peripheral Vein Pharmacokinetics of Raltitrexed in Swine After the Administration of a Hepatic Arterial Infusion |
| Authors | Zhu, Linzhong Zheng, Nan Li, Xingang Zhang, Xiaofeng |
| Affiliation | Peking Univ, Dept Intervent Therapy, Key Lab Carcinogenesis & Translat Res, Minist Educ Beijing,Canc Hosp & Inst, Beijing 100142, Peoples R China Peking Univ, Natl Drug Clin Trial Ctr, Key Lab Carcinogenesis & Translat Res, Minist Educ Beijing,Canc Hosp & Inst, Beijing 100142, Peoples R China Capital Med Univ, Beijing Friendship Hosp, Dept Pharm, Beijing 100050, Peoples R China Beijing Obstet & Gynecol Hosp, Dept Radiol, Beijing 100006, Peoples R China |
| Keywords | Raltitrexed hepatic arterial infusion hepatic artery peripheral vein pharmacokinetics two-compartmental model swine |
| Issue Date | 2019 |
| Publisher | CURRENT DRUG METABOLISM |
| Abstract | Background: Hepatic Arterial Infusion (HAI) with raltitrexed has become an effective treatment for hepatocellular cancer and colorectal cancer liver metastases. However, traditional Body Surface Area (BSA)-based dosing is unsafe or ineffective, and a more accurate model-based approach is required. Methods: In this study, domestic swine were given 1 mg or 4 mg raltitrexed administered by an HAI with infusion times of 30, 60 and 120 min. Hepatic Artery (HA) and Peripheral Vein (PV) samples were collected, and a two-compartment model with an elimination pathway was established to describe the in vivo behavior of raltitrexed. Results: The clearance was 0.27 L/min, and the volumes of distribution were 0.35 and 6.65 L for the HA and PV compartments, respectively. The goodness-of-fit plots and visual predictive checks suggested that the proposed pharmacokinetic model agreed well with the observations. Conclusion: The pharmacokinetic model could be helpful in quantitatively describing the detailed processes of raltitrexed activity administered by HAI and determining an appropriate dosing regimen for preclinical and clinical studies. |
| URI | http://hdl.handle.net/20.500.11897/551715 |
| ISSN | 1389-2002 |
| DOI | 10.2174/1389200220666190618100847 |
| Indexed | SCI(E) |
| Appears in Collections: | 北京肿瘤医院 |
