{"title":"他克莫司与利特莫韦和唑类抗真菌药物在造血干细胞移植后的相互作用:回顾性观察分析。","authors":"Yuri Shinogi, Toshinori Hirai, Miki Ishibashi, Kazuko Ino, Isao Tawara, Takuya Iwamoto","doi":"10.1002/prp2.1120","DOIUrl":null,"url":null,"abstract":"<p><p>Tacrolimus interacts with letermovir and azole antifungals, whereas letermovir has nonuniform effects on the pharmacokinetics of azole antifungals. We retrospectively investigated the interaction of tacrolimus (continuous infusion) with letermovir considering co-administered azole antifungals in adult hematopoietic stem cell transplantation patients. The extent of intraindividual variation in the ratio of tacrolimus concentration to dose normalized by body weight (C/D ratio) was investigated. The correlation between the C/D ratio and estimated glomerular filtration rate (eGFR) was analyzed. In 35 patients (795 points), the C/D ratio was higher in the tacrolimus plus letermovir period than in the tacrolimus alone period (1234.7 [566.2-2721.0] ng/mL/mg/kg vs. 564.4 [245.3-1861.3] ng/mL/mg/kg, p < .001). This trend was observed when co-administered with azole antifungals (n = 30, 1285.5 [662.7-2506.7] ng/mL/mg/kg vs. 547.1 [245.3-1861.3] ng/mL/mg/kg, p < .001), but not without azole antifungals (n = 5, 809.9 [566.2-1573.3] ng/mL/mg/kg vs. 616.1 [350.6-979.8] ng/mL/mg/kg, p = .125). For patients co-administered fluconazole, the tacrolimus C/D ratio increased in patients with letermovir than those without letermovir (n = 28, 1215.0 [662.7-2506.7] ng/mL/mg/kg vs. 529.9 [245.3-1654.4] ng/mL/mg/kg, p < .001). Tacrolimus C/D ratio did not correlate with eGFR under letermovir and fluconazole administrations (y = 0.1x + 1307.1, r = .008, p = .968). Close blood concentration monitoring of intravenous tacrolimus is required when patients administered letermovir and azole antifungals.</p>","PeriodicalId":19948,"journal":{"name":"Pharmacology Research & Perspectives","volume":null,"pages":null},"PeriodicalIF":2.9000,"publicationDate":"2023-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/e7/e0/PRP2-11-e01120.PMC10395274.pdf","citationCount":"0","resultStr":"{\"title\":\"Drug interactions of tacrolimus with letermovir and azole antifungals following hematopoietic stem cell transplantation: A retrospective observational analysis.\",\"authors\":\"Yuri Shinogi, Toshinori Hirai, Miki Ishibashi, Kazuko Ino, Isao Tawara, Takuya Iwamoto\",\"doi\":\"10.1002/prp2.1120\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>Tacrolimus interacts with letermovir and azole antifungals, whereas letermovir has nonuniform effects on the pharmacokinetics of azole antifungals. We retrospectively investigated the interaction of tacrolimus (continuous infusion) with letermovir considering co-administered azole antifungals in adult hematopoietic stem cell transplantation patients. The extent of intraindividual variation in the ratio of tacrolimus concentration to dose normalized by body weight (C/D ratio) was investigated. The correlation between the C/D ratio and estimated glomerular filtration rate (eGFR) was analyzed. In 35 patients (795 points), the C/D ratio was higher in the tacrolimus plus letermovir period than in the tacrolimus alone period (1234.7 [566.2-2721.0] ng/mL/mg/kg vs. 564.4 [245.3-1861.3] ng/mL/mg/kg, p < .001). This trend was observed when co-administered with azole antifungals (n = 30, 1285.5 [662.7-2506.7] ng/mL/mg/kg vs. 547.1 [245.3-1861.3] ng/mL/mg/kg, p < .001), but not without azole antifungals (n = 5, 809.9 [566.2-1573.3] ng/mL/mg/kg vs. 616.1 [350.6-979.8] ng/mL/mg/kg, p = .125). For patients co-administered fluconazole, the tacrolimus C/D ratio increased in patients with letermovir than those without letermovir (n = 28, 1215.0 [662.7-2506.7] ng/mL/mg/kg vs. 529.9 [245.3-1654.4] ng/mL/mg/kg, p < .001). Tacrolimus C/D ratio did not correlate with eGFR under letermovir and fluconazole administrations (y = 0.1x + 1307.1, r = .008, p = .968). 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引用次数: 0
摘要
他克莫司与莱特莫韦和唑类抗真菌药物相互作用,而莱特莫韦对唑类抗真菌药物的药代动力学影响不均匀。我们回顾性地研究了他克莫司(持续输注)与利特莫韦在成人造血干细胞移植患者中联合使用唑类抗真菌药物的相互作用。研究了他克莫司浓度与体重归一化剂量之比(C/D比)的个体变异程度。分析C/D比值与肾小球滤过率(eGFR)的相关性。35例患者(795分)中,他克莫司联合莱特莫韦组C/D比值高于单用他克莫司组(1234.7 [566.2-2721.0]ng/mL/mg/kg vs. 564.4 [245.3-1861.3] ng/mL/mg/kg, p
Drug interactions of tacrolimus with letermovir and azole antifungals following hematopoietic stem cell transplantation: A retrospective observational analysis.
Tacrolimus interacts with letermovir and azole antifungals, whereas letermovir has nonuniform effects on the pharmacokinetics of azole antifungals. We retrospectively investigated the interaction of tacrolimus (continuous infusion) with letermovir considering co-administered azole antifungals in adult hematopoietic stem cell transplantation patients. The extent of intraindividual variation in the ratio of tacrolimus concentration to dose normalized by body weight (C/D ratio) was investigated. The correlation between the C/D ratio and estimated glomerular filtration rate (eGFR) was analyzed. In 35 patients (795 points), the C/D ratio was higher in the tacrolimus plus letermovir period than in the tacrolimus alone period (1234.7 [566.2-2721.0] ng/mL/mg/kg vs. 564.4 [245.3-1861.3] ng/mL/mg/kg, p < .001). This trend was observed when co-administered with azole antifungals (n = 30, 1285.5 [662.7-2506.7] ng/mL/mg/kg vs. 547.1 [245.3-1861.3] ng/mL/mg/kg, p < .001), but not without azole antifungals (n = 5, 809.9 [566.2-1573.3] ng/mL/mg/kg vs. 616.1 [350.6-979.8] ng/mL/mg/kg, p = .125). For patients co-administered fluconazole, the tacrolimus C/D ratio increased in patients with letermovir than those without letermovir (n = 28, 1215.0 [662.7-2506.7] ng/mL/mg/kg vs. 529.9 [245.3-1654.4] ng/mL/mg/kg, p < .001). Tacrolimus C/D ratio did not correlate with eGFR under letermovir and fluconazole administrations (y = 0.1x + 1307.1, r = .008, p = .968). Close blood concentration monitoring of intravenous tacrolimus is required when patients administered letermovir and azole antifungals.
期刊介绍:
PR&P is jointly published by the American Society for Pharmacology and Experimental Therapeutics (ASPET), the British Pharmacological Society (BPS), and Wiley. PR&P is a bi-monthly open access journal that publishes a range of article types, including: target validation (preclinical papers that show a hypothesis is incorrect or papers on drugs that have failed in early clinical development); drug discovery reviews (strategy, hypotheses, and data resulting in a successful therapeutic drug); frontiers in translational medicine (drug and target validation for an unmet therapeutic need); pharmacological hypotheses (reviews that are oriented to inform a novel hypothesis); and replication studies (work that refutes key findings [failed replication] and work that validates key findings). PR&P publishes papers submitted directly to the journal and those referred from the journals of ASPET and the BPS