Simple Formula to Calculate Half-Life
The most straightforward formula to calculate half-life (t½) is: t½ = 0.693 / k, where k is the elimination rate constant. 1
Basic Calculation Methods
Standard Formula
- Half-life equals 0.693 (natural log of 2) divided by the elimination rate constant (k): t½ = 0.693/k 1
- The elimination rate constant k can be derived from the slope of the natural log of plasma concentration versus time 1
- This formula applies to first-order elimination kinetics, which describes most drugs 1, 2
Alternative Calculation from Clearance
- Half-life can also be calculated as: t½ = (0.693 × Volume of Distribution) / Clearance 1
- This relationship is particularly useful when clearance and volume of distribution are known 1
Critical Adjustments for Renal or Hepatic Impairment
Renal Impairment Considerations
- For renally eliminated drugs, reduced glomerular filtration rate (GFR) directly prolongs half-life 1
- Creatinine clearance (CrCl) serves as a proxy for renal function and affects drug elimination 1
- Example: Dabigatran has a half-life of 14-17 hours with normal renal function (CrCl ≥80 mL/min), but increases to 16-18 hours with moderate impairment (CrCl 30-50 mL/min) 1, 3
- Use the CKD-EPI equation for most accurate eGFR estimation in adults, as it outperforms creatinine-based equations alone 1
Hepatic Impairment Considerations
- For drugs with high hepatic extraction (diltiazem, lidocaine, metoprolol, propranolol, verapamil), reduced hepatic blood flow prolongs half-life 1
- Drugs with low intrinsic clearance (like warfarin) depend more on hepatic enzyme activity than blood flow 1
- Phase I metabolism (CYP450-mediated) decreases 20-50% with age and hepatic disease, increasing half-life of highly metabolized drugs 1
Practical Clinical Application
Bedside Estimation
- For clinical purposes, if you know the dosing interval at steady-state where peak concentration is twice the first-dose peak, this equals the "operational multiple dosing half-life" 4, 5
- This operational half-life is often more clinically relevant than terminal half-life for predicting drug accumulation 4, 5
Single Sample Method
- When only one blood sample is available, half-life can be estimated if the sample is drawn at or after three half-lives post-dose 6, 7
- This approach is particularly valuable in critically ill patients where multiple sampling poses risks 6, 7
- The later the sampling point, the more accurate the half-life estimate 7
Common Pitfalls to Avoid
- Do not assume terminal half-life predicts drug accumulation at steady-state—the operational multiple dosing half-life is often significantly shorter 4, 5
- Do not rely solely on serum creatinine in elderly patients—reduced muscle mass can mask renal impairment, leading to underestimation of half-life prolongation 1
- Do not use population average half-lives for dose adjustments in patients with organ impairment—calculate patient-specific values when possible 6
- For two-compartment models, MRT (mean residence time) may be greater or less than half-life depending on the fraction of drug eliminated in the distribution phase 2