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TheRedLob t1_j6ed2bg wrote

I did my PhD on this, but for living patients ;)

As you say, there are many factors at play, most importantly distribution volume and drug elimination rate. For all of these factors, you can estimate the typical value and the between-individual variability in the population. We call this a population pharmacokinetic model.

With just a single concentration, you assume this person is a "typical individual". You can back-calculate (based on time of death and time of taking the drug) what the dosage typically could have been. You need the administration time though, the time of death, and you better hope the drug concentration remained stable between time of death and time of autopsy. In clinical studies, blood samples are often stored in solid co2 (-80C), and for good reason.

Using the known variability in the population, you can also give a confidence range for your initial dose prediction. You can make predictions more precise by adding information. Bodyweight influences likely drug distribution volume. A second drug (with known dosage and administration time) could help you too.

Usually, this technique is done for drugs that need to be in a precise concentration range. Give a dose, measure concentration, estimate blood volume and calculate the optimal dose for that patient. We call this Model Informed Precision Dosing: MIPD. You can apply the same in autopsies, but I doubt it is routinely applied. Cool question!

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Optimistic__Elephant t1_j6fcjaq wrote

Somewhat relatedly, how come prescription medicine isn’t sized based on the patient weight?

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TheRedLob t1_j6fqqwt wrote

Some drugs are!

Drugs that work with a single dose for everyone are more convenient. Yes, paracetamol 1g tablet may give lower concentrations in someone weighing 140kg vs 70kg, but these drugs are safe and effective over a wide range of concentrations.

Some drugs have a more narrow therapeutic range. We either adapt the dose by bodyweight (paracetamol for children is a prime example!), but can adapt to many many more covariates. Even race can play a role, with some mutations increasing drug metabolism being less prevalent in whites, so more risk of overdose. And sometimes, it is not the dose but the frequency that is adapted (1g 2 times vs 3 times per day)

In some cases, no covariates exist. You either measure concentration in the blood, or you measure the effect (eg drugs for sedating during surgery).

Sure, it would be more optimal to also dose paracetamol that way. Dose high,measure concentration in blood and adapt. You would get faster pain relief with lower risk. But would you come to hospital and pay a team of doctors/engineers to do that, for a simple headache?

That was the question I answered with my PhD: is all that hastle worth it? For some life saving drugs with strong side effects and very variable metabolism, it is.

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dromaeovet t1_j6gl154 wrote

As a vet, the question of “why aren’t human medications doses based on weight” has always baffled me! We dose nearly everything in mg/kg because patient sizes are so different. We have some rules of thumb for species with a fairly standard size (mg/cat is a common one!) but I typically double check the mg/kg dose anyway.

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sat1vum t1_j6hhp3y wrote

In humans small differences in weight are usually not that big of a deal. Other factors like liver function or wether you take an oral drug with or without food introduce much more variability. Even if weight varies greatly between subjects, it’s often because of a higher fat mass. Most drugs don’t distribute into fatty tissue that well and so in those cases a weight based dose might over dose someone. Fat free mass is sometimes used but often not really needed. In children we do use a weight based dose though.

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bruce_kwillis t1_j6g027h wrote

To add in, at least in the US it's a little less to do with the therapeutic range and a whole lot more with the safety range,and what was tested during clinical testing.

Since we often look at log differences in the clinic when it comes to safety, you can safely assume for most drugs prescribed at x mg/day that they will still be efficacious in a fairly large range of adult weight ranges.

However, especially with some drugs as you have indicated, this isn't the case. Personally I am often worried with something like hormonal birth control, which we are constantly trying to reduce the dose to limit side effects, however there is efficacy issues with larger patients.

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r7-arr t1_j6exqzy wrote

Aren't you constrained by having tests for all the chemicals in the drug?

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TheRedLob t1_j6frjrr wrote

Yes! In general, you cannot bring a drug to market without being able to measure it in blood reliably. But those tests are often not available in eg a rural hospital. This field is therefore a real interplay between doctors, statistici an/software engineers, and bio-assay manufacturers.

Now for illegal designer drugs, that is a completely different ball game. They may even be built to evade detection.

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