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In this one-compartment model, the most common model of elimination is first order kinetics, where the elimination of the drug is directly proportional to the drug's concentration in the organism. This is often called linear pharmacokinetics , as the change in concentration over time can be expressed as a linear differential equation d C d t ...
Most drugs are eliminated from the blood plasma with first-order kinetics. For this reason, when a drug is introduced into the body at a constant rate by intravenous therapy, it approaches a new steady concentration in the blood at a rate defined by its half-life. Similarly, when the intravenous infusion is ended, the drug concentration ...
In first-order (linear) kinetics, the plasma concentration of a drug at a given time t after single dose administration via IV bolus injection is given by; = / where: C 0 is the initial concentration (at t=0)
Clearance is variable in zero-order kinetics because a constant amount of the drug is eliminated per unit time, but it is constant in first-order kinetics, because the amount of drug eliminated per unit time changes with the concentration of drug in the blood. [3] [4]
An example of a drug where first-pass metabolism is a complication and disadvantage is in the antiviral drug remdesivir. Remdesivir cannot be administered orally because the entire dose would be trapped in the liver with little achieving systemic circulation or reaching target organs and cells (for example, cells infected with SARS-CoV-2 ).
The first order rate constants k12 and k21 describe exchange between the two compartments. Note that kp = k12, kd = k21. (D) Two compartment model defined in terms of the drug amount, where Nbl is the amount of drug in blood (mg), and Np is the amount in peripheral tissue (mg).
Many drugs follow a biphasic elimination curve — first a steep slope then a shallow slope: STEEP (initial) part of curve —> initial distribution of the drug in the body. SHALLOW part of curve —> ultimate excretion of drug, which is dependent on the release of the drug from tissue compartments into the blood.
Zero-order absorption: rate of absorption is constant. A common example is continuous intravenous infusion. First-order absorption: rate of absorption is proportional to the amount of drug remaining to be absorbed. Representative examples include typical cases of oral administration, subcutaneous injection, and intramuscular injection.