Concentration zones visualised
MEC MTC
Window width = MTC / MEC. A ratio <2 defines a narrow therapeutic index drug ↗.
Therapeutic ranges for commonly monitored drugs
| Drug | Therapeutic range | Toxic threshold | Monitoring metric |
|---|---|---|---|
| Digoxin | 0.5–2 ng/mL | >2 ng/mL | Serum digoxin level (trough) |
| Lithium | 0.6–1.2 mmol/L | >1.5 mmol/L | 12 h post-dose serum Li |
| Phenytoin | 10–20 mg/L (total) | >20 mg/L | Total + free level (if hypoalbuminaemic) |
| Carbamazepine | 4–12 mg/L | >12 mg/L | Trough serum level |
| Valproate | 50–100 mg/L | >100 mg/L | Trough serum level |
| Vancomycin | AUC/MIC 400–600 mg·h/L | AUC >650 mg·h/L | Bayesian AUC estimation |
| Cyclosporine | Protocol C₀ 100–200 ng/mL (typical) | Nephrotoxicity, hypertension | C₀ trough or AUC₀₋₁₂ |
| Tacrolimus | 5–15 ng/mL (transplant-dependent) | Nephrotoxicity, neurotoxicity | C₀ trough |
| Warfarin | INR 2–3 (most indications) | INR >4 → bleeding risk | INR (not plasma level) |
| Gentamicin | Peak 5–10 mg/L; trough <2 mg/L | Trough >2 mg/L → nephrotoxicity | Peak and trough levels |
Frequently asked questions
What is the therapeutic window of a drug?
The therapeutic window is the plasma concentration range between the minimum effective concentration (MEC) — the lowest concentration producing the desired effect — and the minimum toxic concentration (MTC). Drugs within this range are both effective and tolerated. The ratio MTC/MEC defines the width: a ratio <2 defines a narrow therapeutic index (NTI) drug ↗. Use the half-life calculator to understand concentration-time profiles and how dosing affects time in range. See NCBI StatPearls — PK basics ↗ for the concentration-effect framework.
What is the difference between therapeutic window and therapeutic index?
Therapeutic window (clinical): the plasma concentration range MEC–MTC for an individual patient. Therapeutic index (TI) (pharmacological): TD₅₀ / ED₅₀ — the ratio of the median toxic dose to the median effective dose, derived from population-level dose-response data. A TI close to 1 is dangerous; a TI >100 indicates a very wide safety margin. Narrow therapeutic index (NTI) is defined by FDA as TI <2 for AUC and Cmax in bioequivalence studies. In everyday clinical language, "therapeutic window" and "therapeutic range" are used interchangeably with the measured plasma concentration target range. See FDA NTI BE guidance ↗.
Which drugs have the narrowest therapeutic windows clinically?
Clinically narrowest windows: Digoxin 0.5–2 ng/mL (renal elimination; interactions with amiodarone, verapamil; toxicity — nausea, AV block, arrhythmia); Lithium 0.6–1.2 mmol/L (NSAIDs, thiazides ↑ levels; toxicity — tremor, confusion, nephrogenic DI); Phenytoin 10–20 mg/L (zero-order kinetics at upper range — see first-order vs zero-order); Warfarin INR 2–3; Vancomycin AUC/MIC 400–600; Tacrolimus/Cyclosporine protocol-dependent. All require TDM ↗. The ISMP high-alert medication list ↗ highlights these drugs for extra safety precautions.
How does the therapeutic window change with patient characteristics?
Patient-specific factors that narrow or shift the effective therapeutic window: Renal function — drugs cleared renally (digoxin, vancomycin, lithium, gentamicin) accumulate when GFR falls; use the creatinine clearance calculator. Hepatic function — high-extraction drugs (lidocaine, morphine) have reduced first-pass metabolism in liver disease; see hepatic dosing guide. Protein binding — hypoalbuminaemia (sepsis, cirrhosis, nephrotic syndrome) increases free drug fraction for highly bound drugs (phenytoin, valproate); interpret total levels with caution. Genetics — CYP2D6 PM/UM shifts exposure for codeine, tramadol, metoprolol. Age — paediatric PK guide and elderly GFR reduction.