J Gynecol Oncol.
2022 Sep;33(5):e56. 10.3802/jgo.2022.33.e56.
Rotational intraperitoneal pressurized aerosol chemotherapy with paclitaxel and cisplatin: pharmacokinetics, tissue concentrations, and toxicities in a pig model
- Park SJ
1 - Lee EJ2
- Seol A3
- Park S4
- Ham J5
- Yim GW6
- Shim SH7
- Lim W8
- Chang SJ9
- Song G5
- Park JW10
- Kim HS1
- on behalf of the Korean Rotational Intraperitoneal pressurized Aerosol chemotherapy (KoRIA) Trial Group
- Affiliations
-
- 1Department of Obstetrics and Gynecology, Seoul National University College of Medicine, Seoul, Korea
- 2Department of Obstetrics and Gynecology, Chung-Ang University Hospital, Seoul, Korea
- 3Department of Obstetrics and Gynecology, Korea University College of Medicine, Seoul, Korea
- 4Department of Plant & Biomaterials science, Gyeongsang National University, Jinju, Korea
- 5Institute of Animal Molecular Biotechnology and Department of Biotechnology, College of Life Sciences and Biotechnology, Korea University, Seoul, Korea
- 6Department of Obstetrics and Gynecology, Dongguk University College of Medicine, Goyang, Korea
- 7Department of Obstetrics and Gynecology, Research Institute of Medical Science, Konkuk University School of Medicine, Seoul, Korea
- 8Department of Biological Sciences, Sungkyunkwan University, Suwon, Korea
- 9Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Ajou University School of Medicine, Suwon, Korea
- 10Department of Surgery, Seoul National University College of Medicine, Seoul, Korea
- KMID: 2537904
- DOI: http://doi.org/10.3802/jgo.2022.33.e56
Abstract
Objective
We used paclitaxel and cisplatin, known to be effective in intraperitoneal chemotherapy, in a novel prototype of rotational intraperitoneal pressurized aerosol chemotherapy (RIPAC) and evaluated the pharmacokinetics, tissue concentrations, and toxicities in a pig model.
Methods
We developed RIPAC, including the nozzle with the conical pendulum motion, and used 10% of intravenous doses of paclitaxel and cisplatin. We used high-performance liquid chromatography followed by tandem mass spectrometry to analyze serum and tissue concentrations. We applied a non-compartment model to study pharmacokinetics to analyze the time-dependent serum concentrations measured before RIPAC to 48 hours. We evaluated the difference in tissue concentrations between twelve peritoneal regions by the modified peritoneal cancer index. For evaluating toxicities, we observed hepatic and renal function until 4 days after RIPAC.
Results
Six pigs underwent RIPAC using paclitaxel (n=3) and cisplatin (n=3). The peak serum concentration (Cmax) and the area under the curve were higher for cisplatin, while the time to the peak serum concentration (Tmax) was longer for paclitaxel. Moreover, the parietal peritoneum showed higher tissue concentrations than the visceral peritoneum, and the ratio of tissue to serum concentrations using Cmax was higher for paclitaxel (172.2–6,237.9) than for cisplatin (0.1–9.3). However, there were no renal and hepatic toxicities after RIPAC with paclitaxel or cisplatin.
Conclusion
Delayed absorption of paclitaxel sprayed by RIPAC into the peritoneum to the bloodstream may lead to higher tissue concentrations at different regions and lower serum concentrations than cisplatin.
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