Canonical Question
PK – Metabolism
Master answer
| Zero order kinetics | First order kinetics | |
|---|---|---|
| Definition | Rate of elimination = dP/dT = constant | dC/dt = kC |
| Elimination = constant | Rate of Elimination = Cl x C | |
| Explanation | • Elimination of a drug from the body is saturable. • The rate of change of concentration with time is constant (v) | • Rate of Elimination of a drug from the body is proportional to the concentration. • Elimination is equal to the area under the curve of the concentration versus time curve after dose of drug is administered. |
| Example | Phenytoin when plasma [ ] > 10 μg/mL Other examples include • Ethanol • Aspirin | Phenytoin when plasma [ ] > 10 μg/mL |
| Implication | • Small changes in doses or adjustment of other medications effecting pheytoin metabolism • Narrow therapeutic index, and zero order kinetics and therapeutic drug monitoring is important | Elimination is dependent on blood flow (ie high extraction ratio) |
Phenytoin or Aspirin
- Display Michaelis-Menten kinetics
- Zero order at high concentration when enzyme saturate
- First order at low concentrations
- Thus highly variable plasma concentrations
\[{Rate\;of\;elimination}={{\delta P} \over {\delta t}}={{V_{max} \times S} \over {K_m + S}}\]
- Where
- S is the substrate concentraton
- Vmax is the maximum elimination capacity
- Km is the drug concentration at which the rate of elimination is half of the maximal rate.
Gladwin 2016
Exam appearances
| Exam | Exact wording | Relationship | Success |
|---|---|---|---|
| 2009B Q17 | Explain the difference and the clinical relevance, between zero and first order pharmacokinetics. (60% marks) Give an example that is relevant to intensive care practice. (40% marks) | historical_member | — |