I’m taking a drug that is causing profound nausea and vertigo called Liraglutide and I’m having difficulties with pharmacokinetics. I have basic background in pharmaco from studying it for two semesters in uni decades ago but didn’t continue with the field so my skills are a little rusty.
I know the T1/2 and Vd (from UptoDate and the drug monograph) and I’m following [this](https://en.wikipedia.org/wiki/Volume_of_distribution#Sample_values_and_equations) but I still can’t solve it? I actually tried to find the Vd myself but to find it you need C0 and to find C0 you need Vd so it becomes a never-ending cycle. Are these formulas even correct? Because from what I remembered, they’re not at all — I studied a different type of formula.
The T1/2 of the drug is 13 hours and I’m supposed to inject myself once a day which I make sure is at least 35 hours and beyond from the last injection but I still experience the same side effects, sometimes even worse, which is why I’m trying to find out the drug elimination rate constant but I just can’t figure it out good god. Can someone simplify it for me? ~~Or is there possibly a calculator that does this for me?~~
Also, why do some drugs like Diazepam and Haloperidol have a T1/2 that becomes even longer after chronic dosing? Does it have to do with it being hydrophilic or hydrophobic?
Lastly, is there a formula to predict drug plasma concentration (doesn’t have to be particularly Liraglutide) after chronic dosing without having to get your blood drawn and analysed in a lab? And does side effects begin at Cmin and appear at it’s worst at Cmax, or am I wrong?
Edit: No, no calculators. I want it the manual way, tell me the formulas and I’ll fill in the gaps myself!
Edit 2: I tried [this](https://observablehq.com/@henryaj/drug-plasma-level-calculator) calculator and they told me that after 11 hours has elapsed (now) the dose in my body left is 0mg. Well of course it is — my daily dose is 0.6mg!
In: Biology
It depends on your albumine levels and how fast your liver and kidneys eliminate the active metabolite. No drug formula can be as precise as periodically checking your blood levels. If you have liver/kidney problems and or have higher albumine levels, the drug’s biological half-life can be prolonged. If you take other drugs that get eliminated by the same enzymes ( cytochrome P450 family, for example), then neither of them will work as intended.
There is no absolute parallel link between the length of the **therapeutical effect** of the drug and its hydrophilic/phobic nature. Some drugs are amphiphilic, some start as hydrophobic and then turn hydrophilic or vise-versa. Some work better when ingested, some work only when injected. General rule of thumb is that a lipophilic drug needs more time to work but then works longer.
Drugs that are hydrophilic usually stay in the bloodstream and then get excreted by the kidneys unchanged (renal elimination decreases half-life). When the drug is protein bound ( like Liraglutide), the renal elimination is slower because of the size of the molecule being bigger than the capillary wall of the kidney. Some small-moleculed drugs can also be reabsorbed (tubular reabsorption), thus increasing T1/2.
Drugs that are lipophilic tend to distribute in fat and muscle tissue **and stay longer in the body**. They get metabolized by the liver into more polar molecules and then either released in the gut to be reabsorbed into the bloodstream (which could increase half-life, if the polar metabolite is still an active drug) or be directly excreted by the kidneys.
Haloperidol and Diazepam are lipophilic, heavily protein bound medications that get accumulated in the brain and liver after prolonged use and that’s why they get metabolized by Cytochrome P450 at a much slower rate as to when used just once.
I suggest you check your blood levels to see if your blood sugar isn’t too low or if the dosage is appropriate. Maybe ask your doctor if Metformin or other antidiabetics are more suitable if the adverse effects don’t disappear after a few weeks.
I’m kind of confused about what you’re asking for… Do you want the elimination rate constant? That doesn’t tell you much other than allowing you to calculate other parameters (eg, half – life). The site you linked has all the correct equations.
There are equations that can predict plasma concentrations, but they’re only predictions. You can predict the drug concentration, but every person doesn’t have the same body composition so it will vary based on a number of factors. In practice, the equations are used to appropriately dose certain drugs but are not used in place of physical tests.
Your question about diazepam and haloperidol has to do with distribution. Being hydrophobic drugs, they are largely distributed into the peripheral compartment. This results in a drug repository that extends the half – life after chronic use.
If you’re having these symptoms, you should bring it up with your doctor. There are many other options for diabetes treatment that might give you similar benefit with minimal side effects.
Edit: the elimination rate constant is simply ln(2)/(T1/2). Just plugging in a T1/2 of 13h gives you a ke of 0.053 h-1
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