Half-life
Quick Definition
Half-life (t½) is the time required for the plasma concentration of a drug to decrease by 50%. Half-life determines dosing frequency, time to steady state, and time to drug clearance after discontinuation.
In Depth
The half-life of a drug is a fundamental pharmacokinetic property that governs dosing schedule, time to steady state, and time to clearance.
A drug reaches approximate steady state after 4-5 half-lives of repeated dosing. After discontinuation, the drug is approximately 97% cleared after 5 half-lives.
Examples relevant to this site:
- Sildenafil: half-life ~4 hours. On-demand dosing only — peak effect within 1 hour, clinical window ~4 hours. - Tadalafil: half-life ~17.5 hours. Both on-demand (24-36 hour clinical window) and daily low-dose (steady state in 5-7 days) dosing schedules supported. - Dutasteride: half-life ~5 weeks. After discontinuation, drug is detectable for months. - Semaglutide: half-life ~7 days. Once-weekly dosing; steady state after 4-5 weeks. - Tirzepatide: half-life ~5 days. Once-weekly dosing; steady state within 4 weeks. - Finasteride: half-life ~6-8 hours, but the biological effect (DHT suppression) persists longer. Daily dosing standard.
Half-life is determined by the rate of metabolism (typically by the liver) and clearance (kidney, biliary). It is influenced by patient factors such as hepatic function, renal function, age, and drug-drug interactions.
The clinical implications:
- Long half-life drugs produce stable plasma concentrations with infrequent dosing but cannot be quickly removed if a side effect emerges. - Short half-life drugs require more frequent dosing but offer rapid offset. - Half-life is one factor in choosing between alternatives in a drug class — for example, sildenafil vs tadalafil for ED, where the half-life difference is the dominant practical distinction.
Related Terms
Area Under the Curve
Area Under the Curve (AUC) is a measure of total drug exposure over time, calculated as the integral of the plasma concentration vs time curve. AUC is used in pharmacokinetics to compare drug formulations, doses, and bioequivalence.
Bioavailability
Bioavailability is the fraction of an administered dose of unchanged drug that reaches systemic circulation. By definition, intravenous administration has 100% bioavailability; other routes (oral, transdermal, intramuscular) have varying bioavailability based on absorption, first-pass metabolism, and other factors.
PDE5 Inhibitor
A PDE5 inhibitor is a medication that inhibits the enzyme phosphodiesterase type 5, which degrades cyclic guanosine monophosphate (cGMP) in vascular smooth muscle. The class is FDA-approved for erectile dysfunction and pulmonary arterial hypertension, and includes sildenafil, tadalafil, vardenafil, and avanafil.