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-   -   Cyto-Toxicity and dosage (http://www.physicsforums.com/showthread.php?t=474713)

Jennifer100 Feb21-11 12:59 AM

Cyto-Toxicity and dosage
 
If you had the following information on Cyto-Toxicity of a drug:

the relative viability on (human) cell lines are high (Above 90%) even under higher concentrations of the compound (hundreds of micro-molar). Cyto-toxicity should be minor concern.

What would you assume to be the maximum safest dose of that drug? (For a daily dose, and also for a one-time-only dose) Based only on the above information.Im only asking for the best educated guess based on the above info that you can come up with, since you obviously could never know how safe the drug was without years of testing

For example, would it be highly probable that 250 mg would be safe? Or would it be fairly impossible to make any good guesses only using the above information

mtc1973 Feb21-11 06:28 AM

Re: Cyto-Toxicity and dosage
 
Human cell lines are mostly cancer cell lines - and extremely good at transporting drugs out of them - and have a much higher toxic/lethal dose than 'real' cells. Therefore, you could never infer from a cell line the information you are trying to infer.
There just is no way to infer - hence why the process includes years of testing.

Jennifer100 Feb22-11 02:33 PM

Re: Cyto-Toxicity and dosage
 
if you are just looking to find out more info on what the odds are that a specific amount of a specific compound would kill a human is it more efficient to test the compound on a dog or a rat? What I mean is, why would testing on a rat be more efficient than testing on a dog? (To get information on that) Is it just that there are more rules in place against testing on dogs? What animal would be more efficient to test on than a dog or a rat?

nismaratwork Feb22-11 02:41 PM

Re: Cyto-Toxicity and dosage
 
I don't see any way around what mtc1973 said, none. Pharmacokinetics/dynamics are just not that simple... which is why we still test and STILL end with recalled drugs.

Jennifer100 Feb26-11 01:28 AM

Re: Cyto-Toxicity and dosage
 
what are the reasons that people prefer to test drugs on beagles rather than other dogs? What are the pros of testing drugs on beagles instead of other dogs?

mtc1973 Feb26-11 10:21 AM

Re: Cyto-Toxicity and dosage
 
Standard genetic line - like any other animal model. You use a model that has been bred so that all members are simiar and carry similar genetic code - that way experiments are less confounded by genetic variability. The dog doesnt matter as long as they have been bred carefully. You could take a mongrel and back cross it and breed it to a genetically similar breed (and I dont mean to a beagle!) - but that has been done already with pedigree dogs so why reinvent the wheel. Also beagles are naturally social and love packs - very little fighting between them when housed together because of their very social nature. It means keeping them in large groups communally is logistically easier.

nismaratwork Feb26-11 04:22 PM

Re: Cyto-Toxicity and dosage
 
I'd add, they have a BBB that is closer to human than some other breeds, such as Collies.

Jennifer100 Feb26-11 09:02 PM

Re: Cyto-Toxicity and dosage
 
why not use a goat, or pig, or something instead of a dog?
assuming they were fine with being housed together and that the ones you are using are have genetic code that is similiar to each other's

Jennifer100 Feb26-11 09:03 PM

Re: Cyto-Toxicity and dosage
 
Specifically what did you mean by BBB? Did you mean they have closer genes to a human than a collie does?

Jennifer100 Feb26-11 09:05 PM

Re: Cyto-Toxicity and dosage
 
also can they just put the drugs into meat and feed it to the dog that way- or does giving the drug to the dog with food change the drug somehow?

nismaratwork Feb26-11 09:07 PM

Re: Cyto-Toxicity and dosage
 
Quote:

Quote by Jennifer100 (Post 3160333)
why not use a goat, or pig, or something instead of a dog?
assuming they were fine with being housed together and that the ones you are using are have genetic code that is similiar to each other's

Goats are not used in such a fashion, but pigs are very close to being perfect human analogues for GI and Vascular issues. In fact, drugs are tested on a number of animals.

As for BBB: Blood Brain Barrier; Collies have a notoriously permeable one. I was illustrating why a standard genetic line in any given animal is key as a control/test.


For the record... I hate the idea of animal testing, but that doesn't stop me from knowing the protocols. Usually, cell lines, mice, pigs and dogs, and then if necessary primates, and finally humans. Never forget that last one, because for all the rest, every drug is a fundamental test of its long-term effects in an unpredictable population.

Jennifer100 Feb28-11 06:18 PM

Re: Cyto-Toxicity and dosage
 
If anthraquinone derivatives, or a different component of a compound, are being used to achieve a certain effect but that effect is very sensitive to a slight modification of the anthraquinone derivatives, or another component, of a compound that is being used to achieve that effect,
what does that mean?

Does it mean the compound would not be consumed orally, because the stomach would modify that compound? Does that mean the compound can't be eaten with food food, because if it was on top of food or mixed in or something that would modify the compound? Would the stomach modify the compound enough that it wouldn't work- would it have to be adminstered through iv, or nothing? Or does that just relate to things like the temperature of the compound? Im just confused about what "sensitive to a slight modification" means in that context

nismaratwork Feb28-11 07:42 PM

Re: Cyto-Toxicity and dosage
 
Quote:

Quote by Jennifer100 (Post 3163870)
If anthraquinone derivatives, or a different component of a compound, are being used to achieve a certain effect but that effect is very sensitive to a slight modification of the anthraquinone derivatives, or another component, of a compound that is being used to achieve that effect,
what does that mean?

Does it mean the compound would not be consumed orally, because the stomach would modify that compound? Does that mean the compound can't be eaten with food food, because if it was on top of food or mixed in or something that would modify the compound? Would the stomach modify the compound enough that it wouldn't work- would it have to be adminstered through iv, or nothing? Or does that just relate to things like the temperature of the compound? Im just confused about what "sensitive to a slight modification" means in that context

Hmmmm... is this an academic question, or a 'homework-help' question? How to proceed really depends on that, because there is an easy answer, but if this is meant to be a learning experience, you can still get help here... just not the flat-out answer.

I will say this... One of the uses for anthraquinone is a laxitive... what does that tell you?

Jennifer100 Feb28-11 08:54 PM

Re: Cyto-Toxicity and dosage
 
its an academic question not a homework help question;
but would it mean the compound would have to be administered via the blood, and not through eating it? Would that also mean it couldn't be taken with food? Since the effect is sensitive to modifications to components of the compound? Im just confused by what that means

Or does it just mean, don't change the temperature and other things about the components of the compound since the effects could be changed by modification to the components of the compound?

nismaratwork Feb28-11 09:11 PM

Re: Cyto-Toxicity and dosage
 
Quote:

Quote by Jennifer100 (Post 3164121)
its an academic question not a homework help question;
but would it mean the compound would have to be administered via the blood, and not through eating it? Would that also mean it couldn't be taken with food? Since the effect is sensitive to modifications to components of the compound? Im just confused by what that means

Or does it just mean, don't change the temperature and other things about the components of the compound since the effects could be changed by modification to the components of the compound?

It's very hardy, and very bioavailable; up to 91% throgh oral administration. In short, this just means that you need to match your desired outcome with this multi-use drug, to serum levels.

Lets say you're using this to treat asthma... well you'd use oral administration to achieve around ~80%-~90% availability which is what you want, and doesn't present a metabolic risk. As the dose of this rises, the available compound for treating asthma (anthraquinone 2-carboxylic acid) has an inverse relationship to dosage given orally.

So, if you need to have a very HIGH level maintained, you'd need to buffer it, or administer it through other means.

Jennifer100 Mar26-11 01:37 PM

Re: Cyto-Toxicity and dosage
 
what are the reasons to not use purebred huskies when testings drugs/compounds on dogs?

Jennifer100 Mar29-11 12:38 AM

Re: Cyto-Toxicity and dosage
 
Is it true that the more genetically similar the animal is to humans, the more it can tell you about how toxicity of a drug will affect a human? therefore, would testing on cats and dogs yield more accurate results than testing on rabbits, when it comes to testing on animals to try to predict human toxicity of a drug?

Ryan_m_b Mar29-11 02:25 AM

Re: Cyto-Toxicity and dosage
 
Quote:

Quote by Jennifer100 (Post 3216700)
Is it true that the more genetically similar the animal is to humans, the more it can tell you about how toxicity of a drug will affect a human? therefore, would testing on cats and dogs yield more accurate results than testing on rabbits, when it comes to testing on animals to try to predict human toxicity of a drug?

It really depends on the drug. Ideally you want to be as close as possible with genetics to a human but you also want to be as close as possible in proteomics. Some species are less related genetically but are better at simulating specific systems or tissues. Other species such as drosophila have only 50% genetic similarity and 70% protein (if i remember that correctly, its been a long while since ive worked in a drosophila lab!) but are useful for development and genetic studies. They're also quite good because they breed in large numbers and through generations very quickly.

Drug testing is a very wide field, it's not really as simple as "test the closest to human". If we had humans that we tested on theres a lot of work we couldnt do, such as how genetic diseases progress across generations unless you want to go to the expense and time of breeding thousands of people for hundreds of years.

I wish we didnt have to test on animals but there is no alternative at the moment. Hopefully over the next several decades our progress with tissue engineering and regenerative medicine will provide us with fully formed in vitro tissues/organs to test on instead.


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