I know that as volumes of distribution increase they correspond to the blood, then the vascular rich group (heart, kidneys, liver, brain if BBB permeable), then muscle then adipose. But things like flow should also be taken into account. So are drugs usually distributed in a similar manner to blood, vascular rich group, etc?
$\begingroup$
$\endgroup$
4
-
$\begingroup$ I guess this is about the distribution of a drug within the body? $\endgroup$– ArsakCommented Apr 24, 2019 at 11:30
-
$\begingroup$ Volume of distribution is a property of the drug and not the tissue. Your question is unclear. $\endgroup$– WYSIWYGCommented Apr 24, 2019 at 13:29
-
$\begingroup$ Thank-you for letting me know, but can you explain further? I know that the volume of distribution is unique to a drug, but high volumes of distribution indicate the drug is preferentially stored in adipose; and that low volumes indicate it is retained in the blood. I am asking where the bone marrow would fit in the progression above. i.e. Are low Vd drugs stored in blood AND bone marrow? or Does the bone marrow retain drugs with a similar capacity to the VRG? $\endgroup$– Roby VicaryCommented Apr 25, 2019 at 3:13
-
$\begingroup$ @RobyVicary Vd is an indicative of the drug solubility. Drugs with high water solubility are enriched in blood whereas the ones high lipid solubility (and hence low water solubility) end up in adipose. There are other factors too apart form solubility. However, pharmacodynamics is not simply determined by drug solubility. Your question should be rephrased and perhaps you should ask how much percentage of a certain drug in blood is present in bone marrow. Most bone marrows have good vasculature; so I would guess that bone marrow should have almost the same concentration as the blood. $\endgroup$– WYSIWYGCommented Apr 25, 2019 at 12:39
Add a comment
|
1 Answer
$\begingroup$
$\endgroup$
How are drugs distributed into any tissue, and what affects it? Note that there are no general answers, and that this is highly dependent on the drug in question.
Active or passive transport
Is your drug a substrate for any uptake or efflux transporters that may affect the distribution?
Solubility
Lipophilic drugs will generally have a greater volume of distribution, as there is more passive diffusion into tissue.
Blood flow
How much drug is presented to the area in question? Tissue with greater perfusion (e.g. kidneys) will have a greater exposure to the drug. Look up the well-stirred model.
Relating this to the blood marrow
So what should you research in order to answer your question?
- What are the physiochemical properties of the drug in question? How are these compared to other drugs where the bone marrow is a target?
- Is the drug a substrate for any relevant transporters in the tissue of interest?
You should also look up if there are any physiologically-based pharmacokinetic (PBPK) models for your drug or drugs with similair physiochemical properties. Some of these are free, and allow you to make general assumptions about the distribution of the drug.
