What is a typical drug concentration in the body

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Discussion Overview

The discussion revolves around determining typical physiological concentrations of pharmaceutical drugs in the body, exploring factors that influence these concentrations, and the implications for drug design, particularly for large molecules like antibodies. Participants share insights from their research and experiences, while seeking to understand the variability in drug concentrations based on different parameters.

Discussion Character

  • Exploratory
  • Technical explanation
  • Conceptual clarification
  • Debate/contested
  • Mathematical reasoning

Main Points Raised

  • One participant notes a range of LD50 concentrations from 1 to 100 μM in literature and questions if ~1 μM is a reasonable concentration to consider.
  • Another participant suggests that micrograms per liter could be a reasonable estimate based on typical drug concentrations.
  • A participant provides specific dosage examples for LSD and aspirin, highlighting the variability in drug dosages based on molecular weight.
  • Concerns are raised about the volume of distribution for drugs, particularly large molecules like antibodies, and whether they are localized in plasma or distributed throughout the body.
  • Questions are posed regarding the retention of drugs in the body post-administration and the variability in excretion rates, with uncertainty about average half-lives.
  • One participant emphasizes the complexity of drug concentration due to factors like metabolism, distribution spaces, and drug-specific properties such as size and solubility.
  • There is a suggestion to consult pharmacology textbooks for foundational knowledge on drug absorption, distribution, metabolism, and excretion (ADME).

Areas of Agreement / Disagreement

Participants express varying views on the typical concentrations of drugs and the factors influencing them. There is no consensus on a specific concentration figure or the assumptions regarding drug retention and distribution, indicating ongoing uncertainty and exploration of the topic.

Contextual Notes

Limitations include the dependence on specific drug properties, variability in metabolism and distribution, and the lack of consensus on average half-lives and retention times for different drugs.

Who May Find This Useful

This discussion may be useful for researchers and students in pharmacology, drug design, and related fields who are interested in understanding drug concentrations and their implications in physiological contexts.

Roo2
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I'm trying to figure out a typical range of physiological concentrations for pharmaceutical drugs. I'm looking through papers that report candidate drugs administered to cell cultures; these papers report LD50 concentrations anywhere from 1 to 100 μM. I don't have any pharmacology experience so I don't know how these numbers compare to commercially available drugs (I realize that different drugs have different toxicities but there must be some ballpark figure). I calculated one such figure by using this clinical study for Herceptin, which reported a serum concentration of 123 μg/mL at a dosage of 2 mg/kg, which I converted to ~0.8 μM (MW 145531.5 g/mol). This seems to be in accord with the dosage recommendation.

Is the ~1 μM figure a good concentration to look for in these papers? If no, why not?

Thanks for any help.
 
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micro gram / Liter sounds reasonable assuming the typical drug is in mg / ml, the average body total water is like 5 L. What kind of research are you working on, can we help?
 
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It depends on the drug. LSD dosages (MW = 323.43) are between 100 and 500 micrograms. A common aspirin (MW = 180.157) is 325 milligrams, and an extra strength aspirin is 500 milligrams.
 
Thanks for the replies. I'm trying to go from weight to concentration... there are a couple confounding factors. If I assume that all of the drug is retained for the first couple hours of dosage, then I'm faced with deciding what volume of water to use. Wiki give a 40L figure for an average male, but only 3 L is plasma, which would contribute to an order of magnitude difference in concentration. Would a large molecule drug (say an antibody) be localized mostly in the plasma, or would it be distributed throughout the body? Antibodies are generally not internalized so intracellular volume wouldn't be accessible, but I don't know enough physiology to decide if there are any other water repositories that would be accessible.

Also, is the assumption that roughly all of the drug is retained for the first few hours after administration a reasonable one? Obviously excretion rates vary by drug but I don't know how much variability there is; would an average half life be on the order of minutes, hours, or days?

I'm working on large molecule drug design but I'm only a new grad student; I'm doing some literature review to assess the feasibility of a project I'm thinking of. As previously stated, the candidate drugs described in the literature I'm reviewing have LD50 values in the 10 - 100 μM range so I'm trying to get a feel for how "good" that is.
 
There are many, many factors that affect the concentration of any given drug in the body and the "space" it is in. By "space" I mean the drug's distribution--does it end up in the extracellular space? Intracellular space? The plasma? Fat? etc. Also how the drug is metabolized is very important. Some drugs are metabolized very fast by the liver, especially when taken orally due to first pass metabolism. Which plays into the bioavailability.

Other things, such as drug specific properties will determine what space the drug occupies. Such as its size, lipid solubility, charge, etc.

If you asking about when a given dose of a drug becomes effective, then you want to look into dose-response curves. Ex:
paraquat.jpg


Really it sounds like you need a good textbook on pharmacology. A general text like Pharmacology: Principles and Practice would be a good primer. Any edition would work. Specifically you want to focus on ADME (absorption, distribution, metabolism and excretion) and pharmacokinetics.
 

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