title: [Pharmacological study and pharmaceutical intervention to reduce intravenous injection-induced vascular injury].
abstract: Intravenous injection often causes vascular injury such as venous irritation, vascular pain, and phlebitis. Vascular injury deteriorates the patient's QOL and sometimes limits the continuation of injection therapy. Pharmaceutical intervention and pharmacological mechanisms used to reduce vascular injury induced by vinorelbine and epirubicin were reviewed. A multivariate logistic regression analysis revealed that the dose of vinorelbine (≥40 mg) was a significant predictor for venous irritation. Alteration of the volume of normal saline for vinorelbine dissolution, from 50 to 100 mL, significantly decreased the grade of venous irritation. On the other hand, the phlebitis scores were significantly higher in patients treated with epirubicin ready-to-use solution compared with lyophilized powder. The change of formulation of epirubicin to lyophilized powder decreased the risk of venous irritation. The concentration inducing 50% cell viability inhibition was lower in the order of vesicant, irritant, and nonvesicant drugs on porcine aorta endothelial cells (PAECs), suggesting that the injuring effects of anticancer drugs on PAECs may be relevant as an indicator of the frequency of their vascular injury. The exposure to vinorelbine of PAECs rapidly depleted intracellular glutathione levels and increased intracellular reactive oxygen species production. Moreover, exposure to epirubicin increased intracellular lipid peroxide levels and enhanced the phosphorylation of p38 mitogen-activated protein kinase. These results demonstrate that oxidative stress plays an important role in vinorelbine- and epirubicin-induced endothelial cell injury, and may therefore increase the potential for vascular injury upon intravenous injection.
authors.affiliation: Department of Pharmacy, Kyushu University Hospital.
authors.forename: Takaaki
authors.initials: T
authors.lastname: Yamada
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D004847:Epithelial Cells / Q000166:cytology; D006801:Humans; D007275:Injections, Intravenous; D057772:Vascular System Injuries / Q000517:prevention & control*; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D048051:p38 Mitogen-Activated Protein Kinases