Wei Xiao-Chen, Zhao Ming-Feng, Xiao Xia
Department of Pharmacy, Tianjin First Central Hospital, Tianjin, PR China.
Department of Hematology, Tianjin First Central Hospital, Tianjin, PR China.
J Infect Chemother. 2024 Mar;30(3):255-257. doi: 10.1016/j.jiac.2023.10.008. Epub 2023 Oct 11.
Posaconazole is a potent, extended-spectrum triazole antifungal used for the treatment and prophylaxis of serious fungal infections. Previous reports have demonstrated hyperlipidemia resulted in significant changes in posaconazole pharmacokinetics and tissue distribution in rats. However, the effect of hyperlipidemia on the pharmacokinetics of posaconazole in patients has not yet been reported. We report a case of a 34-year-old woman who experienced a supratherapeutic posaconazole trough concentration (PTC) associated with hyperlipidemia after haploidentical hematopoietic stem cell transplantation (HSCT). The patient was admitted 13 months after HSCT for recurrent cough and sputum. She was treated with caspofungin due to developing invasive fungal infection of Candida tropicalis. After 10 days, caspofungin was discontinued due to the poor therapeutic efficacy and replaced with amphotericin B. Afterwards, the condition of the patient improved significantly and she was switched to daily oral posaconazole tablet. Therapeutic drug monitoring (TDM) of posaconazole showed a PTC was 3.2 mg/L. After discharge, she continued to receive posaconazole tablet as antifungal treatment. Two months later, laboratory tests at outpatient showed her blood lipid levels were significantly elevated and PTC was increased to 9.38 mg/L. Therefore, the posaconazole tablet was discontinued and she received lipid-lowering therapy. A few days later, the PTC was down to 5.22 mg/L. No medication errors and significant drug interactions were found. Hence, supratherapeutic PTC for this patient may be caused by hyperlipidemia which altered pharmacokinetics of posaconazole. Our findings highlight the need for close TDM in order to avoid supratherapeutic PTC if hyperlipidimia occurs during posaconazole use.
泊沙康唑是一种强效、广谱三唑类抗真菌药物，用于治疗和预防严重的真菌感染。先前的报告表明，高脂血症会导致大鼠体内泊沙康唑的药代动力学和组织分布发生显著变化。然而，高脂血症对患者体内泊沙康唑药代动力学的影响尚未见报道。我们报告了一例34岁女性患者，在单倍体造血干细胞移植（HSCT）后出现高脂血症，其泊沙康唑谷浓度（PTC）高于治疗水平。该患者在HSCT后13个月因反复咳嗽和咳痰入院。由于发生热带念珠菌侵袭性真菌感染，她接受了卡泊芬净治疗。10天后，由于治疗效果不佳，卡泊芬净停药，换用两性霉素B。此后，患者病情显著改善，并改用每日口服泊沙康唑片。泊沙康唑的治疗药物监测（TDM）显示PTC为3.2mg/L。出院后，她继续接受泊沙康唑片作为抗真菌治疗。两个月后，门诊实验室检查显示她的血脂水平显著升高，PTC升至9.38mg/L。因此，停用泊沙康唑片，并接受降脂治疗。几天后，PTC降至5.22mg/L。未发现用药错误和明显的药物相互作用。因此，该患者高于治疗水平的PTC可能是由高脂血症改变泊沙康唑药代动力学所致。我们的研究结果强调，在使用泊沙康唑期间，如果发生高脂血症，需要密切进行TDM，以避免PTC高于治疗水平。
