Increased distribution of carboplatin, an anti-cancer agent, to rat brains with the aid of hyperbaric oxygenation

Abstract

1. The distribution of an anti-cancer agent carboplatin to brains was investigated in combination with hyperbaric oxygenation treatment in rats.

2. After intravenous administration of carboplatin (30 mg kg⁻¹) to male Wistar rats, elimination curves of plasma drug concentrations plotted against a time of 45 min were not different with or without hyperbaric oxygenation (at 0.20–0.25 MPa for last 20 min) treatments.

3. Carboplatin concentrations of livers, lungs and kidneys in each group were similar at the endpoint of hyperbaric oxygenation treatment.

4. Under these atmosphere conditions (at 0.10 MPa), carboplatin concentration was at an undetectable level in rat brains (<0.1 µg g⁻¹ tissue, n = 6). On the contrary, carboplatin was detected in all brains tested at the levels of 0.5 ± 0.3 µg g⁻¹ tissue (mean and standard deviation (SD), n = 6), 0.8 ± 0.5 µg g⁻¹ tissue, and 0.4 ± 0.2 µg g⁻¹ tissue in combination with hyperbaric oxygenation at 0.20, 0.22, and 0.25 MPa, respectively, at the endpoint of hyperbaric oxygenation treatment.

5. The results suggest that carboplatin could be uptaken into rat brains at the detectable levels by the aid of hyperbaric oxygenation, consistently with the reported findings of enhanced transendothelial permeability and improved clinical efficacy of carboplatin combined hyperbaric oxygenation therapy.

Keywords::

• Hyperbaric oxygenation
• carboplatin
• brain

Acknowledgements

The authors would like to thank Yasuyuki Yoshida, Shintaro Gamura, Haruka Yamaguchi, Rina Tanaka and Moe Kinoshita for their help. This study was supported, in part, by the Ministry of Education, Science, Sports and Culture of Japan, the Ministry of Health, Labor and Welfare of Japan.