[Pharmacology] - Pharmacokinetics || Drug Clearance Explained

Over the last few days, I have been discussing pharmacology and I focused on pharmacokinetics. I have been creating content on how drugs are absorbed, distributed, metabolized, and excreted. You can those post on my post, or check below my post, where I will be putting the links to them. Today, I will be discussing Drug Clearance.

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Drug clearance is the rate of elimination of a drug over the concentration of the drug in the plasma. Drug clearance is a way of eliminating the drug. It has to do with the liver metabolizing the drug, and excretion. While there are many drugs to eliminate drugs in the body, the kidney and the liver are the most important organs responsible. The liver is responsible for clearing the hepatic system, while the kidney is responsible for clearing the Renal system. Clearance has to do with the elimination of the plasma of the drug in both the hepatic and renal systems which will give the total number of clearances. In simple terms, clearance is dependent on the function of elimination of drugs, which is dependent on the function of the organs. When there is a dysfunction of the organs of elimination, clearance would reduce leading to the accumulation of the drug. The kidney is the major organ of elimination followed by the liver. If the kidney isn't performing properly the drug will not be cleared, and when the drug is not cleared, the concentration of the drug would begin to increase. Also if the liver is having a type of dysfunction such as cirrhosis, or acute liver failure, the drug will not be eliminated from the body. Clearance can also be determined as the Volume of distribution and the 0.693 divided by the half-life.

Cl = Volume of distribution X 0.693 ÷ T½

Half-life is the time taken for a drug to go from 100% to 50%. When a drug has a high half-life, the denominator in the equation will be high reducing the clearance. When a drug has a short half-life, then the denominator in the equation will reduce increasing the clearance. This shows that clearance and half-life have an inversely proportional relationship.

Cl 1/∝ T½

Elimination Kinetics

Most drugs work on first-order enzymatic kinetics according to biochemical profile but some drugs are zero-order enzymatic kinetics.

First Order enzymatic elimination kinetics
Most drugs operate under the first-order enzymatic kinetic. Their rate of elimination vary but the fraction of drug eliminated per unit of time is constant. For first-order enzymatic kinetics, the half-life is constant. When a drug is given at a 100%, it starts to get eliminated but the rate of how the drug gets eliminated is dependent on the half-life. Since the half-life is constant, a particular percentage of the drug will be eliminated per hour. If the half-life is 50% per hour, then every hour, a drug would have lost 50% of its concentration. If a drug is taken 100mg/l, at 100%, its rate of elimination would reduce by 50% making the drug to be left with 50mg/l, in another hour, the drug would have lost 50% of its concentration, leaving the drug to have 25mg/l, and so on as it will keep decreasing exponentially. In first-order enzymatic kinetics, the amount of drug taken is directly proportional to the rate of elimination. when there is an increase in the number of drugs taken, there will be an increase in the rate of elimination.

Zero Order enzymatic elimination kinetics
With zero-order drug operations, the half-life is variable while the rate of elimination is constant. The amount of drug eliminated per hour is constant but the half-life of the drug is variable. While First order enzymatic elimination kinetics has to do with the percentage rate, zero-order enzymatic elimination kinetics doesn't use a half-life percentage but rather uses an elimination rate. If a person takes 100mg/l of the drug, and the elimination rate is 25mg per hour, then that means that at every 1 hour, 25mg will be eliminated, so the drug will be left with 75mg after an hour, then another 25mg is removed reducing the drug amount to 50mg, and so on until it gets to zero which is linear in graphical representation. In this situation, an increased amount of drugs doesn't mean an increased rate of elimination, as they are independent of one another as the rate of elimination is constant. With zero order drugs, there can be toxicity when the dosage is increased.