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Novel oral formulation of paclitaxel inhibits neointimal hyperplasia in a rat carotid artery injury model.
Dong-Woon Kim1, Jin-Sook Kwon, Young-Gyu Kim
1Department of Internal Medicine, Chungbuk National University, Cheongju, Korea. kdwoon@chungbuk.ac.kr
Circulation
|March 10, 2004
View abstract on PubMed
Summary
Novel oral paclitaxel formulations effectively inhibited neointimal formation in a rat carotid artery injury model. This suggests oral paclitaxel may prevent restenosis in humans with minimal toxicity.
Area of Science:
- Vascular Biology
- Pharmacology
- Drug Delivery Systems
Background:
- Paclitaxel is known to inhibit vascular smooth muscle cell migration and proliferation.
- Neointimal formation after vascular injury is a key factor in restenosis.
Purpose of the Study:
- To evaluate the efficacy of novel oral paclitaxel formulations in preventing neointimal formation.
- To assess the safety and toxicity profile of oral paclitaxel in a rat carotid artery injury model.
Main Methods:
- Rats underwent carotid artery injury and were treated with oral paclitaxel (0, 5, 7.5, or 10 mg/kg) or vehicle for 5 days.
- Neointimal formation and luminal diameter were assessed 11 days post-injury.
- Peak plasma paclitaxel levels were measured.
Main Results:
- Oral paclitaxel significantly increased minimum luminal diameter compared to controls.
- Neointimal formation was significantly reduced in all oral paclitaxel treatment groups.
- Peak plasma levels of paclitaxel were dose-dependent, reaching up to 108 nmol/L.
- Intraperitoneal paclitaxel also demonstrated efficacy in inhibiting neointimal formation.
Conclusions:
- Oral paclitaxel formulations are effective in inhibiting the proliferative response to vascular injury in rats.
- These findings suggest that oral paclitaxel holds potential for preventing human restenosis.
- The study indicated a favorable safety profile with minimal toxicity observed in oral paclitaxel-treated rats.