Pharmacokinetic (PK) Curves
Pharmacokinetic curves sound impressive. How about Maximal Plasma Concentration (CMax), Area Under the Curve (AUC), and Time to Peak Absorption (TMax)? Olympic athletes meets calculus meets pre-race snack uptake – what are we talking about?
You don’t have to be an athletic Nobel Prize winner to begin to follow the trail of why PK curves are important. We all experience the results of these curves, multiple times per day with everything we ingest, inhale, or rub on our skin.
PK parameters are various ways scientists judge how fast, how much, and how long a substance acts on our bodies. Bioactive molecules, whether cannabinoids or Advil or statins or blood pressure meds, are intended to get into blood circulation and reach their site of therapeutic action to have an effect.
The broad and somewhat nebulous concept, bioavailability, is the crux of the matter. The pharmaceutical industry does not use the term because of its vagueness but bioavailability has been embraced by the cannabis industry for the time being.
Cannabinoids are “greasy” fat molecules. The human body is predominantly water, and water and fat don’t mix. Think “oil-vinegar effect”, i.e., what happens when your dressing looks like a chemistry experiment in your refrigerator with two layers of ingredients.
Accordingly, only a surprisingly low percentage of the cannabinoids we consume are bioavailable to affect us humanoids. This applies to the now ordinary cannabinoids like Cannabidiol (CBD) or Delta-9-Tetrahydrocannabinol (THC), the increasingly common “minor cannabinoids” like Cannabigerol (CBG) and Cannabinol (CBN), and the exotic ones like Cannabichromene (CBC), Cannabidivarin (CBDV), or Tetrahydrocannabivarin (THCV).
Cannabinoids have high lipophilicity (“fat loving”) and low hydrophilicity (“water loving”). Lipophilicity (logP) is important and is defined as the estimation of the octanol-water partition coefficient. LogP relates the concentration of solute in octanol (an organic fatty alcohol divided by the concentration of solute in water. LogP involves neutral molecules, and lipophilicity is pH dependent, so the distribution coefficient (logD) is an even better measure of lipophilicity as it relates the concentration of ionized solute in octanol + unionized solute in octanol divided by the cencentration of ionized solute in water + the concentration of unionized solute in water.
For various purposes, we want these cannabinoids in our bloodstream speeding their way to the endocannabinoid system (ECS) and its receptors. But in reality, a small percentage of cannabinoids (based on clinical studies), actually make it into our bloodstreams (maybe 30% via smoking and <10% for edibles).
Therefore, in the world of pharmacology, PK and pharmacodynamic (PD) curves are important tools to determine dosing and serving sizes. These curves apply to whatever mode of delivery is chosen (transdermal, oral, edible, mucosal, inhalation, and intravenous) or if the molecules are enhanced with various technoligies like nano-emulsions and liposomal treatments.
Setting aside potential malignancies and other issues, smoking is an efficient mode of sneaking cannabinoids into your bloodstream. With smoking or vaping, as well as intranasal, sublingual, and other mucosal delivery modes, the liver is not initially involved and there is no metabolic first pass effect. However, once the cannabinoids are in the bloodstream, the blood will soon find its way to the liver.