Influence of CYP3A5 and ABCB1 polymorphisms on the pharmacokinetics of vincristine in adult patients receiving CHOP therapy.

PURPOSE: This study aims to clarify the impact of CYP3A5 and ABCB1 polymorphisms on the pharmacokinetics of vincristine (VCR) in adult patients receiving CHOP therapy. METHODS: Plasma samples were collected immediately after the end of VCR administration and at 1.5, 2.5, 3.5, 5.5, 9.5, 13.5, and 25.5 h after the start of administration. Areas under the plasma concentration-time curves of VCR in the elimination phase (AUC1.5-25.5) were calculated using the linear trapezoidal rule. Half-lives of VCR during the early phase (1.5-5.5 h) and terminal phase (5.5-25.5 h; t1/2γ) were determined according to the log-linear regression of the concentration-time data for at least 3 sampling points. RESULTS: A total of 41 adult patients were enrolled in this study. The median t1/2γ and AUC1.5-25.5 were significantly longer and higher in CYP3A5 non-expressers (CYP3A5*3/*3) than in CYP3A5 expressers (CYP3A5*1/*1 or *1/*3) (21.3 vs 13.8 h, P = 0.005 and 35.5 vs 30.0 ngï½¥h/mL, P = 0.006, respectively). Conversely, there were no significant differences in pharmacokinetic parameters among the ABCB1 c.1236C>T, c.2677G>A/T, c.3435C>T genotype groups. A stepwise selection multiple linear regression analysis showed that the dose of VCR administered and CYP3A5 non-expresser status were independent factors influencing the AUC1.5-25.5 (partial R2 = 0.212, P = 0.002 and partial R2 = 0.143, P = 0.010, respectively). CONCLUSION: The CYP3A5*3 polymorphism was found to be an indicator for predicting exposure to VCR in adult patients receiving CHOP therapy. This information may be useful for the individualization of VCR dosages.

Newly diagnosed extranodal NK/T-cell lymphoma, nasal type, at the injected left arm after BNT162b2 mRNA COVID-19 vaccination.

Anti-SARS-CoV-2 vaccines were developed in response to the coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Although the BNT162b2 mRNA vaccine is effective, adverse effects have been reported. Here, we report a case of extranodal NK/T-cell lymphoma, nasal type (ENKL), of the left arm following BNT162b2 mRNA vaccination. A 73-year-old male presented with a lump in the left arm, which was the site where he received the BNT162b2 mRNA vaccine 3 months prior. He was treated with topical corticosteroids and debridement, but the tumor progressed. Additionally, fever, night sweats, and general fatigue were observed. Laboratory findings included thrombocytopenia, elevated lactate dehydrogenase, and soluble interleukin-2 receptor levels. Skin biopsy led to a diagnosis of ENKL. The patient was treated with a 50% dose of SMILE therapy and radiotherapy, resulting in regression of the tumor. It seems that latent Epstein-Barr virus (EBV)-infected NK/T cells were reactivated by vaccination and contributed to the onset of ENKL. This is the first report of ENKL after BNT162b2 mRNA vaccination. The present case highlights the possible risk of development of malignant lymphoma, including ENKL at the injection site, after BNT162b2 COVID-19 vaccination.

Simultaneous determination of preservatives in beverages, vinegar, aqueous sauces, and quasi-drug drinks by stir-bar sorptive extraction (SBSE) and thermal desorption GC-MS.

A method for the simultaneous determination of seven preservatives - sorbic acid, benzoic acid, and p-hydroxybenzoic acid ethyl, isopropyl, propyl, isobutyl, and butyl esters - in beverages, vinegar, aqueous sauces, and quasi-drug drinks has been developed using the stir-bar sorptive extraction technique then thermal desorption GC-MS analysis. The extraction conditions - pH, sample volume, extraction temperature, salt addition, and extraction time - were examined. d5-Benzoic acid and p-hydroxybenzoic acid sec-butyl ester were added as surrogate internal standards to compensate for the effect of sample matrix and coexisting analytes on the sorptive extraction. The linearity of the method was good over the concentration range from 1 to 1000 microg mL(-1) for sorbic acid, 10-1000 microg mL(-1) for benzoic acid, and 0.1-100 microg mL(-1) for p-hydroxybenzoic acid ethyl, isopropyl, propyl, isobutyl, and butyl esters, and the correlation coefficients were higher than 0.9984. The limit of detection ranged from 0.015 to 3.3 microg mL(-1). The recoveries (95-105%) and precision (RSD: 0.86-6.0%) of the method were examined by analyzing a sparkling soft drink, white wine, red wine, balsamic vinegar, soy sauce, and quasi-drug drink samples fortified at the 5 to 50 microg mL(-1) level.