Zero vs First-order Kinetics

Current · V5 (2025) → B1.iv Historical · V4 (2023) → B.iv 1 exam appearance

2009B Q17

Exam question

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)

CICMWrecks answer

Master answer

Zero-order and first-order elimination — CICMWrecks original diagram

	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
- V_max is the maximum elimination capacity
- K_m is the drug concentration at which the rate of elimination is half of the maximal rate.

Gladwin 2016

Reusable content

Formulae used in this answer

Phenytoin or Aspirin

CWF-0024

{Rate\;of\;elimination}={{\delta P} \over {\delta t}}={{V_{max} \times S} \over {K_m + S}}

Answer by Gladwin

Past papers

Exam appearances

1 appearance

Exam	Exact exam wording	Candidate 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)	22%