Pharmacokinetics of cisplatin in the systemic versus hyperthermic intrathoracic or intraperitoneal chemotherapy.

IF 2.7 4区 医学 Q3 ONCOLOGY
Tao Zhang, Wei Mu, Cheng-Gong Liao, Yan Hou, Jie Song, Wen Hu, Yun Wang, Dongxu Chen, Yu Chen, Linna Liu, Lili Liu
{"title":"Pharmacokinetics of cisplatin in the systemic versus hyperthermic intrathoracic or intraperitoneal chemotherapy.","authors":"Tao Zhang, Wei Mu, Cheng-Gong Liao, Yan Hou, Jie Song, Wen Hu, Yun Wang, Dongxu Chen, Yu Chen, Linna Liu, Lili Liu","doi":"10.1007/s00280-024-04727-8","DOIUrl":null,"url":null,"abstract":"<p><strong>Objective: </strong>To compare the pharmacokinetics and adverse effects of cisplatin administered via intravenous infusion for systemic chemotherapy (SC) versus injection into the perfusate during hyperthermic intrathoracic chemotherapy (HITHOC) or hyperthermic intraperitoneal chemotherapy (HIPEC).</p><p><strong>Methods: </strong>Total 60 patients who received SC, HITHOC, or HIPEC in the Department of Oncology, Tangdu Hospital, were enrolled into this study. After administering same dose of cisplatin (40 mg) via either intravenous infusion (SC group) or injection into the perfusate during the HITHOC or HIPEC procedure, concentration of cisplatin in the plasma as well as in the hyperthermic perfusate at various time points was quantified by HPLC analysis. The area under the plasma or perfusate concentration-time curve over the last 24h dosing interval (AUC<sub>0-24h</sub>), mean residence time over the 24 h (MRT<sub>0-24h</sub>), terminal elimination half-life (t<sub>1/2z</sub>), time to peak concentration (T<sub>max</sub>), apparent clearance (Clz/F), and peak concentration (C<sub>max</sub>) in the perfusate and plasma were compared.</p><p><strong>Results: </strong>In the perfusate, the AUC<sub>0-24h</sub> (64.32 ± 27.12 µg/mL·h) and C<sub>max</sub> (21.62 ± 5.88 µg/mL) were significantly higher in the HITHOC group compared to that in the HIPEC group (31.68 ± 13.29 µg/mL·h and 16.96 ± 5.54 µg/mL, respectively, p ≤ 0.01). In contrast, MRT<sub>0-∞</sub>, t<sub>1/2z</sub>, and Clz/F were significantly lower in the HITHOC group compared to that in the HIPEC group (p < 0.01). In the plasma, average AUC<sub>0-24h</sub> and C<sub>max</sub> of the HITHOC group were 2.57 ± 0.55 µg/mL·h and 0.26 ± 0.08 µg/mL, respectively, which were significantly lower than that of systemic chemotherapy (SC) group (3.26 ± 0.56 µg/mL·h and 0.69 ± 0.14 µg/mL, respectively, p < 0.01), but no difference compared to that of HIPEC group (3.02 ± 0.52 µg/mL·h and 0.40 ± 0.15 µg/mL, respectively, p > 0.05). In contrast, MRT<sub>0-24h</sub> and T<sub>max</sub> in the plasma of HITHOC group were significantly longer compared to that of SC group (p < 0.05), but no significant difference compared to that of HIPEC group (p > 0.05). Absolute bioavailability of cisplatin in the thoracic (HITHOC group) and abdominal (HIPEC group) cavities was 20 and 10 times higher than that in the blood administered intravenously (SC group), respectively. There was no significant difference in the incidence of adverse events among the three groups (p < 0.05).</p><p><strong>Conclusion: </strong>The current study demonstrated that, in the perfusate, AUC<sub>0-24h</sub> and C<sub>max</sub> of cisplatin was significantly higher in the group of HITHOC compared to that of HIPEC, and that, in the plasma, AUC<sub>0-24h</sub> and C<sub>max</sub> of cisplatin was lower in the group of HITHOC compared to that of HIPEC or SC group. This study provided pharmacokinetic evidence to further support the concept that topical application of chemotherapeutic drug through minimally invasive HITHOC or HIPEC may enhance local exposure compared to systemic chemotherapy for the patients with malignant pleural effusion or ascites.</p>","PeriodicalId":9556,"journal":{"name":"Cancer Chemotherapy and Pharmacology","volume":"95 1","pages":"13"},"PeriodicalIF":2.7000,"publicationDate":"2024-12-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11671569/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Cancer Chemotherapy and Pharmacology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1007/s00280-024-04727-8","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"ONCOLOGY","Score":null,"Total":0}
引用次数: 0

Abstract

Objective: To compare the pharmacokinetics and adverse effects of cisplatin administered via intravenous infusion for systemic chemotherapy (SC) versus injection into the perfusate during hyperthermic intrathoracic chemotherapy (HITHOC) or hyperthermic intraperitoneal chemotherapy (HIPEC).

Methods: Total 60 patients who received SC, HITHOC, or HIPEC in the Department of Oncology, Tangdu Hospital, were enrolled into this study. After administering same dose of cisplatin (40 mg) via either intravenous infusion (SC group) or injection into the perfusate during the HITHOC or HIPEC procedure, concentration of cisplatin in the plasma as well as in the hyperthermic perfusate at various time points was quantified by HPLC analysis. The area under the plasma or perfusate concentration-time curve over the last 24h dosing interval (AUC0-24h), mean residence time over the 24 h (MRT0-24h), terminal elimination half-life (t1/2z), time to peak concentration (Tmax), apparent clearance (Clz/F), and peak concentration (Cmax) in the perfusate and plasma were compared.

Results: In the perfusate, the AUC0-24h (64.32 ± 27.12 µg/mL·h) and Cmax (21.62 ± 5.88 µg/mL) were significantly higher in the HITHOC group compared to that in the HIPEC group (31.68 ± 13.29 µg/mL·h and 16.96 ± 5.54 µg/mL, respectively, p ≤ 0.01). In contrast, MRT0-∞, t1/2z, and Clz/F were significantly lower in the HITHOC group compared to that in the HIPEC group (p < 0.01). In the plasma, average AUC0-24h and Cmax of the HITHOC group were 2.57 ± 0.55 µg/mL·h and 0.26 ± 0.08 µg/mL, respectively, which were significantly lower than that of systemic chemotherapy (SC) group (3.26 ± 0.56 µg/mL·h and 0.69 ± 0.14 µg/mL, respectively, p < 0.01), but no difference compared to that of HIPEC group (3.02 ± 0.52 µg/mL·h and 0.40 ± 0.15 µg/mL, respectively, p > 0.05). In contrast, MRT0-24h and Tmax in the plasma of HITHOC group were significantly longer compared to that of SC group (p < 0.05), but no significant difference compared to that of HIPEC group (p > 0.05). Absolute bioavailability of cisplatin in the thoracic (HITHOC group) and abdominal (HIPEC group) cavities was 20 and 10 times higher than that in the blood administered intravenously (SC group), respectively. There was no significant difference in the incidence of adverse events among the three groups (p < 0.05).

Conclusion: The current study demonstrated that, in the perfusate, AUC0-24h and Cmax of cisplatin was significantly higher in the group of HITHOC compared to that of HIPEC, and that, in the plasma, AUC0-24h and Cmax of cisplatin was lower in the group of HITHOC compared to that of HIPEC or SC group. This study provided pharmacokinetic evidence to further support the concept that topical application of chemotherapeutic drug through minimally invasive HITHOC or HIPEC may enhance local exposure compared to systemic chemotherapy for the patients with malignant pleural effusion or ascites.

顺铂在全身与胸内或腹腔热化疗中的药代动力学。
目的:比较顺铂在全身化疗(SC)中静脉输注与在胸内高温化疗(HITHOC)或腹腔高温化疗(HIPEC)中灌注的药代动力学和不良反应。方法:选择唐都医院肿瘤科接受SC、HITHOC或HIPEC治疗的患者60例。通过静脉输注(SC组)或HITHOC或HIPEC过程中注入相同剂量的顺铂(40mg)后,通过HPLC分析定量血浆中顺铂以及不同时间点的热灌注液中的顺铂浓度。比较最后24小时给药间隔内血浆或灌注液浓度-时间曲线下面积(AUC0-24h)、24小时内平均停留时间(MRT0-24h)、终末消除半衰期(t1/2z)、到达峰值浓度时间(Tmax)、表观清除率(Clz/F)、灌注液和血浆中峰值浓度(Cmax)。结果:灌注液中,HITHOC组AUC0-24h(64.32±27.12µg/mL·h)和Cmax(21.62±5.88µg/mL)显著高于HIPEC组(31.68±13.29µg/mL·h和16.96±5.54µg/mL, p≤0.01)。HITHOC组MRT0-∞、t1/2z、Clz/F均显著低于HIPEC组(p 0-24h、Cmax分别为2.57±0.55µg/mL·h、0.26±0.08µg/mL),显著低于全身化疗(SC)组(3.26±0.56µg/mL·h、0.69±0.14µg/mL, p 0.05)。相比之下,HITHOC组血浆MRT0-24h和Tmax明显长于SC组(p 0.05)。顺铂在胸腔(HITHOC组)和腹腔(HIPEC组)的绝对生物利用度分别比静脉给血(SC组)高20倍和10倍。结论:本研究表明,在灌注液中,HITHOC组顺铂的AUC0-24h和Cmax明显高于HIPEC组,在血浆中,HITHOC组顺铂的AUC0-24h和Cmax明显低于HIPEC组或SC组。本研究提供的药代动力学证据进一步支持了化疗药物通过微创HITHOC或HIPEC局部应用比全身化疗对恶性胸腔积液或腹水患者增加局部暴露的观点。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
求助全文
约1分钟内获得全文 求助全文
来源期刊
CiteScore
6.10
自引率
3.30%
发文量
116
审稿时长
2.5 months
期刊介绍: Addressing a wide range of pharmacologic and oncologic concerns on both experimental and clinical levels, Cancer Chemotherapy and Pharmacology is an eminent journal in the field. The primary focus in this rapid publication medium is on new anticancer agents, their experimental screening, preclinical toxicology and pharmacology, single and combined drug administration modalities, and clinical phase I, II and III trials. It is essential reading for pharmacologists and oncologists giving results recorded in the following areas: clinical toxicology, pharmacokinetics, pharmacodynamics, drug interactions, and indications for chemotherapy in cancer treatment strategy.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
copy
已复制链接
快去分享给好友吧!
我知道了
右上角分享
点击右上角分享
0
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术官方微信