Pelvic irradiation modulates the pharmacokinetics of cisplatin in the plasma and lymphatic system
Journal
American Journal of Translational Research
Journal Volume
7
Journal Issue
2
Pages
375-384
Date Issued
2015
Author(s)
Abstract
Background: Cisplatin (CDDP) is employed to enhance radiotherapy’s (RT) effect for various cancers. However, the effects of local RT on chemotherapeutics in the plasma and lymphatic system remain unclear. Here, we evaluated the influence of pelvic irradiation on the pharmacokinetics (PK) of CDDP using rats as an experimental model. Methods and Materials: RT with 2 Gy and 0.5 Gy were delivered to the whole pelvis of Sprague-Dawley rats. CDDP at 5 mg/kg and 10 mg/kg was intravenously infused 24 hours after radiation for the plasma and lymphatic system, respectively. The pharmacokinetics of CDDP in the plasma and lymphatic system were calculated. Results: Compared with sham-irradiated controls, the whole pelvic irradiation increased the area under the concentration versus time curve (AUC) of CDDP (5 mg/kg) in the plasma by 80% at 0.5 Gy and 87% at 2 Gy, respectively. In contrast, the AUC of CDDP decreased in bile by 13% at both dose levels. Intriguingly, RT could also increase the AUC of CDDP (10 mg/kg) in the lymphatic fluid by 87% at 2 Gy. In addition, the AUC in CDDP without and with RT was 2.8-fold and 3.4-fold greater for the lymph system than for the plasma, respectively. Conclusions: A local pelvic RT could modulate the systemic PK of CDDP in both the plasma and lymphatic fluids of the rats. The RT-PK phenomena are worth further investigation. ? 2015, E-Century Publishing Corporation. All rights reserved.
Subjects
Cisplatin (CDDP); Concurrent chemoradiation therapy (CCRT); Pharmacokinetics; Radiosensitivity; RT-PK
SDGs
Other Subjects
cisplatin; adult; animal experiment; animal tissue; area under the curve; Article; controlled study; drug blood level; elimination half-life; elimination rate constant; high performance liquid chromatography; irradiation; lymphatic system; male; maximum plasma concentration; mean residence time; nonhuman; pelvis; plasma; plasma clearance; radiosensitivity; rat; volume of distribution at steady-state; Rattus
Publisher
E-Century Publishing Corporation
Type
journal article