ABSTRACT
BACKGROUND: Dexamethasone (DEX) induces CYP3A activity in a concentration-dependent manner. However, no study has examined changes in the blood concentration of CYP3A substrate drugs when DEX is administered at high doses. Herein, we present a case in which tacrolimus (TAC), a typical CYP3A substrate drug, was co-administered with a chemotherapy regimen that included high-dose DEX. CASE PRESENTATION: A 71-year-old woman underwent liver transplantation for hepatocellular carcinoma 18 years prior to her inclusion in this case study. She was receiving TAC orally at 2 mg/day and had a stable trough blood concentration of approximately 4 ng/mL and a trough blood concentration/dose (C/D) ratio of approximately 2. The patient was diagnosed with post-transplant lymphoproliferative disease (histological type: Burkitt's lymphoma) after admission. Thereafter, the patient received cyclophosphamide-prednisolone (CP), followed by two courses of R-HyperCVAD (rituximab, cyclophosphamide, doxorubicin, vincristine, and DEX) and R-MA (rituximab, methotrexate, and cytarabine) replacement therapy. DEX (33 mg/day) was administered intravenously on days 1-4 and days 11-14 of R-HyperCVAD treatment, and aprepitant (APR) was administered on days 1-5 in both courses. The TAC C/D ratio decreased to approximately 1 on day 11 during both courses, and then increased. Furthermore, a decreasing trend in the TAC C/D ratio was observed after R-MA therapy. The decrease in the TAC C/D ratio was attributed to APR administration rather than to DEX. CONCLUSION: The induction of CYP3A activity by a high dose of DEX may not be strong. The pharmacokinetic information on DEX and in vitro enzyme activity induction studies also suggested that CYP3A activity induction is not prominent under high-dose DEX treatment.
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 (CLP,app) values of the antineoplastic agents based on their PRs at 240 min (PR240) and assessed the relationship between CLP,app and physicochemical parameters [molecular weight (MW) and logarithm of octanol-water partition coefficient (LogP)]. RESULTS: The CLP,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 CLP,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 (PR240 > 10 ng/min/cm2), moderate (PR240 < 10 ng/min/cm2), 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.
ABSTRACT
BACKGROUND: Medical gloves are an important piece of personal protective equipment that prevents exposure to antineoplastic agents. The permeability of medical gloves to antineoplastic agents is a crucial factor in the appropriate selection of gloves. However, the relationship between glove permeability and material type, thickness, and surface treatment is poorly understood. METHODS: A continuous flow in-line cell device was used for the evaluation of the permeation of five antineoplastic agents (etoposide, cyclophosphamide, doxorubicin hydrochloride, paclitaxel, and fluorouracil) through medical gloves. Medical gloves made of three types of materials (chlorinated latex, non-chlorinated latex, and nitrile) were subjected to a permeability test. The antineoplastic agents in test solutions were tested at the highest concentrations employed in general clinical practice. Then, the relationship between glove thickness and permeability was assessed using chlorinated latex gloves with thicknesses of 0.1, 0.15, 0.2, and 0.1 mm × 2 (to represent the practice of "double gloving"). RESULTS: Only cyclophosphamide and fluorouracil showed detectable permeation through the tested latex gloves. The permeability of chlorinated latex was lower than that of non-chlorinated latex. Nitrile gloves showed no detectable permeability to any of the five antineoplastic agents tested. The permeability of chlorinated latex gloves depended on the thickness of the gloves; 0.1 mm × 2 (double gloving) exhibited the highest resistance to permeation by antineoplastic agents. CONCLUSIONS: The permeability of medical gloves was dependent on the type of material and the surface treatment and decreased as the thickness of the glove increased. The double glove was shown to prevent antineoplastic agent permeation more efficiently than did a single glove of the same total thickness. These results provided important information that will guide the appropriate selection of medical gloves.
ABSTRACT
The formulation characteristics of 6 brands of enteric-coated aspirin tablets under unpackaged conditions at 40°C and 60°C for 4 weeks were analyzed. Appearance, salicylic acid content, dissolution rates, and surface properties (by Raman microscopy) were evaluated to determine stability data, taking into account the clinical use of generic drugs. No change in appearance, decomposition, or dissolution rates was observed in unpackaged aspirin tablets stored at 40°C for 4 weeks. However, when stored at 60°C, tablets of 5 of the 6 brands showed whiskers on their surfaces along with an increase in salicylic acid content and a decrease in dissolution rate. Results of Raman mapping on the surface and cross sectional surface of the tablets with whiskers showed a salicylic acid peak associated with storage at 60°C for 4 weeks. However, for tablets from 1 of the 6 brands, no salicylic acid peaks were observed. For this tablet, Raman microscopy revealed 2 layers of film coating, and talc, which greatly affected the stability of the acetylsalicylic acid, was found only in the outer layer film. These results indicated that the protection of compatibility with talc is one of the important factors in enhancement of aspirin tablet stability in this tablet. We concluded that certification of the characteristics associated with stability and formulation is essential for generic drugs, which are not required to undergo stability testing under extreme storage conditions.
