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 À1 kg À1, 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 mg h mL À1, 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 (p50.05). In terms of free Pt concentration, the apparent volume of distribution and clearance rate was statistically different (p50.05). The Pt plasma protein binding ratios in the early dose stages were significantly boosted by the coadministration of ZMYL (p50.01). 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.

Hepatotoxicity and pharmacokinetics of cisplatin in combination therapy with a traditional Chinese medicine compound of Zengmian Yiliu granules in ICR mice and SKOV-3-bearing nude mice

“…In our previous pharmacokinetics studies in normal rats [ 18 ], ZMYL could produce a potential pharmacokinetics drug-herbs interaction on pharmacokinetic parameters of CDDP and plasma protein binding ratios in the early dosing stages (at 0.17, 0.33, 0.5, 1 h after dosing of CDDP). Drugs are used to treat diseases and only patients are the ultimate consumers of drugs, there were some differences in pharmacokinetics process between pathological state and normal condition.…”

“…ZMYL with batch number of 20110526, a finished product, was supplied by the Department of Pharmaceutical, Shanghai Shuguang Hospital Affiliated with Shanghai University of Traditional Chinese Medicine. The preparation process of ZMYL has been described previously [ 18 ]. To prepare of ZMYL, Astragalus membranaceus (Fisch.)…”

“…Full validation of ICP-MS according to the FDA guidelines was, as far as applicable for ICP-MS, performed for the assay [ 18 ]. In this study, the extraction recoveries and matrix effects for tissues (liver, spleen, kidney, and tumor) were validated.…”

“…In our previous pharmacokinetics studies, ZMYL produced a potential drug-herbs interaction on pharmacokinetic parameters of CDDP calculating from the total and free Pt concentration and Pt plasma protein binding ratios in the early stages in normal rats [ 18 ]. However, the pharmacokinetics of drug may be influenced by the pathological status, such as tumor-bearing status [ 19 ], type 2 diabetes [ 20 ] and non-alcoholic fatty liver disease [ 21 ].…”

Pharmacokinetic comparisons by UPLC‐MS/MS of isomer paeoniflorin and albiflorin after oral administration decoctions of single‐herb Radix Paeoniae Alba and Zengmian Yiliu prescription to rats

“…ZMYL (20131108) was prepared according to the previous reported method (Zhang et al ., ) as follows: pieces of A . membranaceus (Fisch.)…”