Babayeva Mariana, Srdanovic Iva
Department of Biomedical and Pharmaceutical Sciences, Touro College of Pharmacy, 3 Times Square, New York, NY, 10036, USA.
J Cannabis Res. 2024 Jun 20;6(1):27. doi: 10.1186/s42238-024-00238-8.
Cannabidiol is highly bound to plasma proteins. Changes in its protein binding can lead to altered unbound plasma concentrations and result in alteration of pharmacological activity of cannabidiol-containing medications. This research has assessed non-linearity of cannabidiol plasma protein binding and the potential effect of tizoxanide on the binding.
Cannabidiol protein binding was evaluated by ultrafiltration technique. Human plasma was spiked with cannabidiol stock solution to produce samples of various concentrations. For interaction study potential interactant tizoxanide was added in each sample. All samples were processed through Amicon Micropartition system and analyzed by HPLC.
The study has detected cannabidiol binding to borosilicate glass (9%) and polyethylene plastics (15%). In the interaction study the mean protein unbound fraction of cannabidiol was 0.05 (5%), indicating no binding interaction between cannabidiol and tizoxanide since cannabidiol unbound fraction without tizoxanide was also 5%. The cannabidiol fraction unbound was more than 2-fold greater at high concentrations compared to low concentrations.
a). At high concentrations cannabidiol plasma protein binding is non-linear. The non-linearity can affect elimination and medicinal effect of cannabidiol drugs. b). Borosilicate and polyethylene containers should be avoided in formulation, packing and administration of cannabidiol-containing medicines to guarantee correct doses. c). Cannabidiol medications can be co-administered with tizoxanide without caution.
大麻二酚与血浆蛋白高度结合。其蛋白结合的变化可导致游离血浆浓度改变，进而引起含大麻二酚药物药理活性的改变。本研究评估了大麻二酚血浆蛋白结合的非线性以及替唑生胺对该结合的潜在影响。
采用超滤技术评估大麻二酚的蛋白结合情况。向人血浆中加入大麻二酚储备液以制备不同浓度的样本。在相互作用研究中，在每个样本中加入潜在相互作用物替唑生胺。所有样本通过密理博微分离系统处理并采用高效液相色谱法进行分析。
该研究检测到大麻二酚与硼硅酸盐玻璃（9%）和聚乙烯塑料（15%）存在结合。在相互作用研究中，大麻二酚的平均蛋白未结合分数为0.05（5%），这表明大麻二酚与替唑生胺之间不存在结合相互作用，因为不含替唑生胺时大麻二酚的未结合分数也是5%。与低浓度相比，高浓度时大麻二酚的未结合分数高出2倍多。
a）在高浓度下，大麻二酚血浆蛋白结合呈非线性。这种非线性可影响大麻二酚药物的消除和药效。b）在含大麻二酚药物的制剂、包装和给药过程中应避免使用硼硅酸盐和聚乙烯容器，以确保剂量准确。c）大麻二酚药物可与替唑生胺联合使用而无需特别注意。
