What is the maximum safe dose for a drug based on its cyto-toxicity and dosage?

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Discussion Overview

The discussion centers around the maximum safe dosage of a drug based on its cytotoxicity and the implications of testing methodologies in drug development. Participants explore the relationship between cell line viability, animal testing, and the complexities of pharmacokinetics and pharmacodynamics.

Discussion Character

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

Main Points Raised

  • One participant suggests that high relative viability in human cell lines indicates minor cytotoxicity, prompting a question about estimating maximum safe doses based on this information.
  • Another participant counters that human cell lines, often cancerous, do not accurately reflect the toxicity levels in actual human cells, emphasizing the need for extensive testing.
  • A participant raises questions about the efficiency of testing drugs on different animal models, specifically comparing rats and dogs, and inquires about the regulatory landscape affecting such choices.
  • Some participants discuss the advantages of using beagles in drug testing, citing their genetic uniformity and social behavior as beneficial factors.
  • There is a mention of the blood-brain barrier (BBB) in relation to different dog breeds, with a focus on how this impacts drug testing relevance.
  • Questions arise regarding the appropriateness of using other animals, like pigs or goats, for drug testing, with some arguing that pigs may serve as better human analogues for certain physiological studies.
  • Several participants express confusion about the implications of slight modifications to drug components, particularly regarding their administration routes and interactions with food.
  • One participant notes that the bioavailability of a compound can influence its administration method, suggesting that high doses may require alternative delivery systems to avoid metabolic risks.

Areas of Agreement / Disagreement

Participants express differing views on the reliability of cell line studies for inferring human drug safety, with some asserting that such inferences are not valid. There is no consensus on the best animal model for testing, as various factors are considered, including genetic uniformity and physiological relevance. The discussion on drug administration routes and the effects of compound modifications remains unresolved.

Contextual Notes

Limitations include the reliance on specific animal models and cell lines, which may not fully represent human responses. The discussion also highlights the complexity of pharmacokinetics and the need for extensive testing protocols, which are not fully addressed in the contributions.

  • #31
I noticed from reading that:

Beagles have a blood brain barrier that is closer to humans than collies
Collies have a notoriously permeable blood brain barrier
So in that regard beagles are better for testing than collies

But what are the upsides and downsides of testing on dogs that are:

jack russel terrier
Huskey
Australian Shepherd
Heeler

and dogs that are a mix of those? For example do huskies also have a notoriously permeable blood brain barrier?
 
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  • #32
Do you mean that, if the effect of a compound is sensitive to modifications of the compound and/or components of the compound; that as the dose of compound rises, the available compound for treating what you're trying to treat has an inverse relationship to dosage given orally. and that as a result, if you need to have a very HIGH level maintained, you'd need to buffer it, or administer it through other means.

Or were you just referring to a specific drug when you said that and not answering my question, specifically, about what a compound (or components of a compound) being sensitive to modifications meant thanks
 

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