Servicio de Farmacia, Hospital Universitario Miguel Servet, Zaragoza, Spain.
Servicio de Farmacia, Hospital Universitario Miguel Servet, Zaragoza, Spain.
Farm Hosp. 2023 Mar-Apr;47(2):T93-T95. doi: 10.1016/j.farma.2023.02.003. Epub 2023 Feb 21.
This case is based on a drug interaction between nirmatrelvir/ritonavir (approved drug for COVID-19) and voriconazole is presented, possibly derived from the bidirectional effect of ritonavir on the 2 main voriconazole metabolizing enzymes (cytochrome P450 3A and 2C19) ritonavir inhibits the former and induces the latter respectively. According to the main pharmacotherapeutic information databases, in the interaction between both drugs, a decrease in the area under the curve of voriconazole is expected due to the inducing effect of its metabolism; however, in the case we present, unexpectedly, a paradoxical effect occurs, according to what is described in literature, with the result of sustained supratherapeutic levels of voriconazole. Given the short treatment period with nirmatrelvir/ritonavir (5 days), the induction effect of ritonavir proposed in the studies on which the recommendations are based, where treatment with ritonavir is longer, does not occur.
本病例介绍了奈玛特韦/利托那韦(一种批准用于 COVID-19 的药物)与伏立康唑之间的药物相互作用,可能源于利托那韦对 2 种主要伏立康唑代谢酶(细胞色素 P450 3A 和 2C19)的双向作用:利托那韦抑制前者,诱导后者。根据主要的药物治疗信息数据库,在这两种药物相互作用中,由于代谢诱导作用,预计伏立康唑的曲线下面积会减少;然而,在我们介绍的病例中,出乎意料地出现了一种矛盾的效应,这与文献中描述的情况一致,结果是伏立康唑的水平持续高于治疗范围。鉴于奈玛特韦/利托那韦的治疗周期较短(5 天),在基于这些建议的研究中,利托那韦的诱导作用不会发生,因为在这些研究中,利托那韦的治疗时间更长。