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Students Questions Answered
- How do you determine what the steady-state dosage should be?
- Depends on the nature of the drug. If your drug has high toxicity or people are prone to get addicted to it, I would recommend a low dosage as the steady-state concentration. Drugs with lower toxicity. One might give a higher steady-state dosage. You need to just put the rationale for picking the dosage. If the idea of the correct steady-state dosage is confusing, think of it as keeping the Cmax at a constant level.
- A student felt that questions 25-27 were confusing. They felt like questions 25 and 26 are asking for physiological effects of gender and age, while question #27 was asked a combination of both things
- Question #25 and #26 are generic questions, while question #27 is referring to your specific situation, which will be an adult woman between ages 35 that weighs 135 lbs. with comorbidities related to the assigned drug.
- A student could not find Anorm or IVnorm in the lecture notes and wanted to know what they were.
- I think it is a mistake in college education that one needs an explicit equation for every situation, but I will go through the process of figuring it out. Thus, going through the lecture notes will no longer be necessary. What does Anorm mean? It means the dose (A) is adjusted for a 70 kg person. Often many oral drugs are given several dosages 300 mg, 500 mg, etc. A reasonable assumption is that the lower dosage is for a 70 kg person that has not been exposed to it. Therefore, if the low dosage (A) is 300 mg, then the normalized dosage is 4.3 mg/kg (i.e., 300 mg/70 kg). For this project, your drug may or may not be IV. Let us assume that it is not an IV drug. What is the relationship between an oral dosage (Aoral) and an IV dosage (AIV)? Aoral * Bioavailability (F) = AIV. Therefore, Aoral,norm * F = AIV,norm. If the bioavailability (F) = 0.8, then AIV,norm=(4.3 mg/kg)*0.8 = 3.4 mg/kg.
- A student was wondering how to calculate a hypothetical IV dose (AIV) from an oral dose (Aoral).
- It is similar to the question above. I would like you to visualize, when you take an Aoral. The Aoral some (hopefully, most) gets absorbed in the small intestines. Some of the Aoral is lost on its way to the systemic circulation. We will call the dose that ends up in the systemic circulation (Asys-circ). The fraction lost is the bioavailability (F). To get the same dose in the systemic circulation AIV will need to be equal to Asys-circ. Therefore, Aoral * F = AIV = Asys-circ.
- Your drug only mentions creatinine clearance, but no renal clearance or total clearance. What are the values of clearance?
- Creatinine is an amino acid waste product, so your body is going to try to get rid of it as fast as possible through the glomerulus. The limitation would be how fast that you can get the creatinine there, which will be limited by the renal blood flow. Therefore, renal clearance (CLR) will be approximately equal to the blood flow to the kidneys or 70 L/hr. If no liver metabolism or hepatic clearance (CLH) are mentioned, then I would presume that they would be ~0.
- Guidelines help give me an expectation of the result.
- IV dosage (AIV) <= oral dosage (Aoral)