Samara E, Bialer M
Department of Pharmacy, School of Pharmacy, Hebrew University of Jerusalem, Israel.
Drug Metab Dispos. 1988 Nov-Dec;16(6):875-9.
Cannabidiol (CBD) is one of the major nonpsychoactive cannabinoids produced by Cannabis sativa L. Recent studies have shown that a dimethylheptyl homolog (DMH) of CBD is more active as an anticonvulsant than is the naturally occurring CBD. In considering DMH as a potential antiepileptic agent, its pharmacokinetics was studied in dogs (N = 8) after both iv (20 mg) and oral (80 mg) administration. After iv administration, DMH was rapidly distributed. DMH has a mean terminal half-life of 2 hr, its plasma levels decline in a biphasic fashion, and its total body clearance is 8.3 liters/hr. This clearance value, after being normalized to blood clearance by the use of mathematical equations, was less than one half of the value of the hepatic blood flow and its extraction ratio (E) by the liver is 0.39, DMH was observed to have a mean volume of distribution of 10 liters (or 0.5 liters/kg). In four of the eight dogs studied, DMH could not be detected in the plasma after oral administration. In the other four, the oral bioavailability was 3, 21, 39, and 43%, respectively. After oral administration, DMH has a low and variable bioavailability, due to a liver first-pass effect and incomplete absorption from the gastrointestinal tract. In comparison with CBD, DMH has a shorter half-life and lower clearance and volume of distribution values, and its liver extraction ratio is about one half that of CBD.
大麻二酚（CBD）是大麻（Cannabis sativa L.）产生的主要非精神活性大麻素之一。最近的研究表明，CBD的二甲基庚基同系物（DMH）作为抗惊厥剂比天然存在的CBD更具活性。在将DMH视为一种潜在的抗癫痫药物时，研究了其在8只犬静脉注射（20mg）和口服（80mg）后的药代动力学。静脉注射后，DMH迅速分布。DMH的平均终末半衰期为2小时，其血浆水平呈双相下降，全身清除率为8.3升/小时。通过数学方程将该清除率值归一化为血液清除率后，小于肝血流量值的一半，其肝脏提取率（E）为0.39，观察到DMH的平均分布容积为10升（或0.5升/千克）。在研究的8只犬中，有4只口服后血浆中未检测到DMH。在另外4只犬中，口服生物利用度分别为3%、21%、39%和43%。口服后，由于肝脏首过效应和胃肠道吸收不完全，DMH的生物利用度较低且变化较大。与CBD相比，DMH的半衰期较短，清除率和分布容积值较低，其肝脏提取率约为CBD的一半。
