Purine antimetabolites associated Pneumocystis jirovecii pneumonia.

PURPOSE: To detect the possible safety signal of purine antimetabolites associated with Pneumocystis jirovecii pneumonia through disproportionality analysis in the FDA Adverse Event Reporting System (FAERS) Database. METHODS: A case/non-case retrospective disproportionality analysis was performed in the publicly available FAERS database using AERSmine (2004Q1-2021Q3). Four models were developed to explore the signal strength of PAs among different populations with possible confounding factors. Reporting odds ratio (ROR) and Proportional reporting ratio (PRR) was used as the data mining algorithm for the analysis. A value of ROR-1.96SE > 1 and PRR ≥ 2 with an associated X2 value of 4 or more was considered the threshold for a signal. RESULTS: A total of 7073 reports associated with Pneumocystis jirovecii pneumonia were present in the database, of which 899 reports were associated with purine antimetabolites. A crude signal strength of ROR 15.76(14.70-16.91) was obtained for purine antimetabolites associated PJP, with the highest signal strength reported with fludarabine and thioguanine [ROR 19.63(17.42-22.13); 19.45(13.21-28.63)]. Stratifying the cases based on autoimmune disorders and the cancer population revealed an ROR of 3.33(2.46-4.50) and 2.93(2.26-3.79) respectively. The highest risk of PJP with use of PAs was observed amongst children with a higher risk of nearly 2 times than the adult population [ROR 11.57(9.16-14.62)]. CONCLUSIONS: Our study provided evidence on the occurrence of PJP with the use of purine antimetabolites among the autoimmune and cancer population. We identified signals for PJP with azathioprine, mercaptopurine, thioguanine, cladribine, fludarabine, and clofarabine. More research with a superior epidemiological study design of a defined population is required to validate these findings.

Transethosome: An ultra-deformable ethanolic vesicle for enhanced transdermal drug delivery.

Drug delivery through the skin improves solubility, bioavailability, and unwanted systemic side effects of the drug. The selection of a suitable carrier is a challenging process. The conventional lipid vesicles have some limitations. They deliver the drug in the stratum corneum and have poor colloidal stability. Here comes the need for ultra-deformable lipid vesicles to provide the drug beyond the stratum corneum. Transethosomes are novel ultra-deformable vesicles that can deliver drugs into deeper tissues. The composition of transethosomes includes phospholipid, ethanol and surfactants. Each ingredient has a pivotal role in the properties of the carrier. This review covers the design, preparation method, characterisation, and characteristics of the novel vesicle. Also, we cover the impact of surfactants on vesicular properties and the skin permeation behaviour of novel vesicles.