Pharmacokinetics of cisplatin in the absence or presence of Zengmian Yiliu granules (a traditional Chinese medicine compound) in rats determined via ICP-MS: An investigation on drug–herb interactions

Abstract

Context: Cisplatin is a highly effective chemotherapeutic agent against many tumors; however, it has potent adverse effects. Zengmian Yiliu granule (ZMYL), a traditional Chinese medicine (TCM) compound, has been clinically used against platinum (Pt)-induced toxicity and to enhance the efficacy of cisplatin.Objective: The study was conducted to investigate the likelihood of potential pharmacokinetics drug–herbs interaction (DHI) between cisplatin and ZMYL.Materials and methods: An improved ICP-MS method combined with ultrafiltration and microwave-assisted digestion was performed to determine the total and free Pt concentrations in rat plasma after intraperitoneal administration of cisplatin (9 mg/kg) or a combined administration with ZMYL (1 g/kg) by gavage.Results: ZMYL produced a potential DHI on the pharmacokinetic parameters of cisplatin, calculated from the total Pt concentration. The clearance rate decreased from 110.52 to 66.12 mLh−1 kg−1, the mean residence time extended from 63.1 to 164.54 h, the area under the plasma concentration–time curve increased from 86.58 to 152.93 µg h mL−1, the elimination half-life extended from 48.38 to 126.4 h, and the elimination rate constant decreased from 0.017 to 0.006 h, in the ZMYL combination group (p < 0.05). In terms of free Pt concentration, the apparent volume of distribution and clearance rate was statistically different (p < 0.05). The Pt plasma protein binding ratios in the early dose stages were significantly boosted by the co-administration of ZMYL (p < 0.01).Discussion and conclusion: ZMYL is a potential complementary and alternative medicine for cisplatin chemotherapy. The therapeutic benefits of ZMYL–cisplatin chemotherapy derived from pharmacokinetic interaction needs further investigation.