Discipline of Clinical Pharmacology, School of Medicine and Public Health, University of Newcastle, Newcastle, New South Wales, Australia.
Discipline of Clinical Pharmacology, School of Medicine and Public Health, University of Newcastle, Newcastle, New South Wales, Australia.
Clin Ther. 2018 Sep;40(9):1442-1447. doi: 10.1016/j.clinthera.2017.12.008. Epub 2018 Jan 6.
Medicinal cannabis is prescribed under the provision of a controlled drug in the Australian Poisons Standard. However, multiple laws must be navigated in order for patients to obtain access and imported products can be expensive. Dose-response information for both efficacy and toxicity pertaining to medicinal cannabis is lacking. The pharmacokinetic properties of cannabis administered by traditional routes has been described but to date, there is no literature on the pharmacokinetic properties of an intraperitoneal cannabinoid emulsion.
A cachectic 56-year-old female with stage IV ovarian cancer and peritoneal metastases presented to hospital with fevers, abdominal distension and severe pain, vomiting, anorexia, dehydration and confusion. The patient reported receiving an intraperitoneal injection, purported to contain 12g of mixed cannabinoid (administered by a deregistered medical practitioner) two days prior to presentation. Additionally, cannabis oil oral capsules were administered in the hours prior to hospital admission.
THC concentrations were consistent with the clinical state but not with the known pharmacokinetic properties of cannabis nor of intraperitoneal absorption. THC concentrations at the time of presentation were predicted to be ~60ng/mL. Evidence suggests that blood THC concentrations >5ng/mL are associated with substantial cognitive and psychomotor impairment. The predicted time for concentrations to drop <5ng/mL was 49days after administration.
The unusual pharmacokinetic properties of the case suggest that there is a large amount unknown about cannabis pharmacokinetic properties. The pharmacokinetic properties of a large amount of a lipid soluble compound given intraperitoneally gave insights into the absorption and distribution of cannabinoids, particularly in the setting of metastatic malignancy.
医用大麻是根据《澳大利亚毒物标准》中规定的管制药物开处方的。然而，为了让患者获得医用大麻，必须遵守多项法律，而且进口产品可能很昂贵。关于医用大麻的疗效和毒性的剂量反应信息都缺乏。传统途径给药的大麻药代动力学特性已有描述，但迄今为止，尚无关于腹腔内大麻素乳剂药代动力学特性的文献。
一名患有 IV 期卵巢癌和腹膜转移的消瘦 56 岁女性因发热、腹胀和严重腹痛、呕吐、厌食、脱水和意识模糊而到医院就诊。该患者报告说，在出现症状前两天，接受了一名未注册医生注射的含有 12 克混合大麻素（据称）的腹腔内注射，此外，在入院前几个小时还口服了大麻油胶囊。
THC 浓度与临床状况一致，但与大麻的已知药代动力学特性或腹腔内吸收不一致。就诊时的 THC 浓度预计约为 60ng/mL。有证据表明，血液中 THC 浓度 >5ng/mL 与明显的认知和精神运动障碍有关。预计浓度降至<5ng/mL 的时间为给药后 49 天。
该病例的不寻常药代动力学特性表明，我们对大麻药代动力学特性的了解还很有限。大量脂溶性化合物腹腔内给药的药代动力学特性提供了关于大麻素吸收和分布的见解，特别是在转移性恶性肿瘤的情况下。
