Prediction of the permeability of antineoplastic agents through nitrile medical gloves by zone classification based on their physicochemical properties

基于理化性质的区域分类法预测抗肿瘤药物透过丁腈医用手套的渗透性

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Abstract

BACKGROUND: Permeability of antineoplastic agents through medical gloves is an important factor that must be considered for the appropriate selection of gloves. However, predicting the permeability of antineoplastic agents through medical gloves based on their physicochemical properties remains difficult. Thus, this study aimed to elucidate the relationship between the physicochemical properties and permeability of antineoplastic agents through medical gloves. Additionally, we tried to predict the risk of permeation of antineoplastic agents through medical gloves based on physicochemical parameters. METHODS: Ten antineoplastic agents (carboplatin, carmustine, cisplatin, cyclophosphamide, doxorubicin, etoposide, fluorouracil, ifosfamide, oxaliplatin, and paclitaxel) with varying physicochemical properties were investigated, and their permeation rates (PRs) through nitrile medical gloves of varying thicknesses (0.05, 0.07, and 0.1 mm) were measured using a continuous flow in-line cell device. We also determined the apparent permeation clearance (CL(P,app)) values of the antineoplastic agents based on their PRs at 240 min (PR(240)) and assessed the relationship between CL(P,app) and physicochemical parameters [molecular weight (MW) and logarithm of octanol-water partition coefficient (LogP)]. RESULTS: The CL(P,app) values of the 10 antineoplastic agents through nitrile medical gloves (0.05 mm thickness) were significantly correlated with their MWs, but not their LogP values (P = 0.026 and 0.39, respectively; Spearman's rank correlation). This finding indicated that the rates of diffusion of the antineoplastic agents in the glove material showed greater effects on CL(P,app) than the rates of absorption into the glove surfaces within 240 min of exposure. We then classified the 10 antineoplastic agents into 3 zones (Zone A, high LogP/low MW drugs; Zone B, high LogP/high MW drugs; and Zone C, low LogP) and found that Zones A, B, and C corresponded to high (PR(240) > 10 ng/min/cm(2)), moderate (PR(240) < 10 ng/min/cm(2)), and low (no detectable permeation) permeation risk, respectively. CONCLUSIONS: The permeation risk of antineoplastic agents through nitrile medical gloves within the actual continuous wearing time in clinical settings could be predicted using MW and LogP values. We believe that the proposed zone classification of antineoplastic agents will be a useful tool for predicting the permeation risk of antineoplastic agents through medical gloves.

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