Sønderskov Marie Bach, Khatir Dinah Sherzad, Kjærgaard Krista Dybtved, Hasselstrøm Jørgen Bo, Sørensen Lambert Kristiansen, Sædder Eva Aggerholm, Andersen Charlotte Uggerhøj
Department of Clinical Pharmacology, Aarhus University Hospital, Aarhus, Denmark.
Department of Biomedicine, Aarhus University, Aarhus, Denmark.
Kidney Int Rep. 2024 Dec 30;10(3):707-719. doi: 10.1016/j.ekir.2024.12.030. eCollection 2025 Mar.
Chronic kidney disease (CKD) affects approximately 10% of the global population and is associated with a large symptom burden. Medicinal cannabis is advised against in patients with severe CKD. However, pharmacokinetic and pharmacodynamic knowledge regarding their use in patients with CKD is lacking.
We aimed to investigate the pharmacokinetics and side effects of a single dose of Sativex, corresponding to 5.4 mg Δ-tetrahydrocannabinol (THC) and 5 mg cannabidiol (CBD), in patients with CKD stages 4 and 5 compared with healthy volunteers (controls). The study was a nonrandomized and unblinded clinical study.
Twenty controls and 29 patients with CKD completed the study. The area under the curve (AUC) for THC (median [interquartile range]) was 2.76 (1.77-3.48), 4.16 (3.35-5.28), and 4.31 (3.16-5.42) h × ng/ml for controls, and for patients with CKD stages 4 and 5, respectively, with significant differences between patients with CKD and controls. AUC for CBD and metabolites, and other pharmacokinetic parameters, such as maximum concentration ( ) and excretion of metabolites in urine were also significantly different between patients with CKD and controls. After 1.5 hours, numeric rating scale (NRS) scores for dizziness were significantly higher for each CKD group compared with controls (mean NRSscores: 0.7 and 1.5 vs. 0.1).
Total exposure to THC, CBD, and metabolites was higher in patients with CKD stages 4 and 5 compared with controls, and side effects may be more pronounced; however, the intersubject variability was high. If cannabis products are administered to patients with severe CKD, caution is needed.
慢性肾脏病（CKD）影响着全球约10%的人口，并伴有巨大的症状负担。重度CKD患者不建议使用药用大麻。然而，关于其在CKD患者中使用的药代动力学和药效学知识尚缺。
我们旨在研究单剂量的赛乐西（相当于5.4毫克Δ-四氢大麻酚（THC）和5毫克大麻二酚（CBD））在4期和5期CKD患者与健康志愿者（对照）中的药代动力学及副作用。该研究为非随机、非盲法临床研究。
20名对照者和29名CKD患者完成了研究。THC的曲线下面积（AUC）（中位数[四分位间距]），对照者为2.76（1.77 - 3.48）小时×纳克/毫升，4期CKD患者为4.16（3.35 - 5.28）小时×纳克/毫升，5期CKD患者为4.31（3.16 - 5.42）小时×纳克/毫升，CKD患者与对照者之间存在显著差异。CBD及其代谢物的AUC以及其他药代动力学参数，如最大浓度（ ）和尿中代谢物排泄量在CKD患者与对照者之间也存在显著差异。1.5小时后，各CKD组头晕的数字评定量表（NRS）评分显著高于对照者（平均NRS评分：0.7和1.5对比0.1）。
与对照者相比，4期和5期CKD患者中THC、CBD及其代谢物的总暴露量更高，且副作用可能更明显；然而，个体间变异性较高。若对重度CKD患者使用大麻产品，需谨慎。
