title: Increased elimination of paclitaxel by magnesium isoglycyrrhizinate in epithelial ovarian cancer patients treated with paclitaxel plus cisplatin: a pilot clinical study.
abstract: Magnesium isoglycyrrhizinate (MI) has been complementarily used for restoring the hepatic impairments caused by taxol plus platinum based chemotherapies in China. Due to the hepatic dependence of paclitaxel elimination, this pilot clinical study aimed to investigate the influence of MI on the pharmacokinetics of paclitaxel in epithelial ovarian cancer patients. During the standard chemotherapy of intravenous paclitaxel (125 mg/m(2) infused over a 3-h period) and intraperitoneal cisplatin (60 mg/m(2)) for patients with FIGO stage II epithelial ovarian cancer, 9 each of total 18 patients were respectively treated with intravenous MI (100 mg) or vehicle control for 4 days. Plasma paclitaxel was analyzed by HPLC and the pharmacokinetic parameters were calculated with non-compartmental analysis. The hematological, hepatic and renal status was monitored before and 3 days after paclitaxel administration. It was observed the terminal t 1/2 and MRT of paclitaxel were significantly (p = 0.002 and 0.001) reduced by MI, respectively, from 11.0 ± 2.2 and 5.6 ± 1.0 h to 7.7 ± 1.7 and 4.0 ± 0.3 h. Hematological toxicity indicated by platelet count and hepatic events marked with ALT, AST and γ-GT were significant in both groups. In spite of the insignificance of decreased system exposure of paclitaxel and recovered hepatic function by MI, they did correlate with each other. It was therefore deduced that the liver toxicities of paclitaxel plus cisplatin chemotherapy potentially decrease hepatic elimination and increase system exposure of paclitaxel, and the recovery of liver function by MI helps to restore hepatic clearance of paclitaxel. The clinical significance of this pharmacokinetic interaction requires further studies with larger population size.
authors.affiliation: Department of Pharmacy, West China Second University Hospital, Sichuan University, No. 20, Section 3, Renminnan Road, Chengdu, 610041, China.
authors.forename: Kai Jie
authors.initials: KJ
authors.lastname: Chen
authors.forename: Wan Yi
authors.initials: WY
authors.lastname: Chen
authors.forename: Xia
authors.initials: X
authors.lastname: Chen
authors.forename: Yi Ming
authors.initials: YM
authors.lastname: Jia
authors.forename: Gui Qin
authors.initials: GQ
authors.lastname: Peng
authors.forename: Li
authors.initials: L
authors.lastname: Chen
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000493:pharmacokinetics*; D019540:Area Under Curve; D000077216:Carcinoma, Ovarian Epithelial; D002851:Chromatography, High Pressure Liquid; D002945:Cisplatin / Q000008:administration & dosage; D004334:Drug Administration Schedule; D004347:Drug Interactions; D005260:Female; D006207:Half-Life; D006801:Humans; D007262:Infusions, Intravenous; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008657:Metabolic Clearance Rate; D008954:Models, Biological; D009367:Neoplasm Staging; D009375:Neoplasms, Glandular and Epithelial / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D017239:Paclitaxel / Q000008:administration & dosage / Q000493:pharmacokinetics; D010865:Pilot Projects; D012503:Saponins / Q000627:therapeutic use*; D014315:Triterpenes / Q000627:therapeutic use*
chemical_list: C521270:18alpha,20beta-hydroxy-11-oxo-norolean-12-en-3beta-yl-2-O-beta-D-glucopyranurosyl-alpha-D-glucopyranosiduronate magnesium tetrahydrate; D012503:Saponins; D014315:Triterpenes; D017239:Paclitaxel; D002945:Cisplatin