maintenance dose

**Definition:** The maintenance dose (MD) is the amount of drug administered at regular intervals (or as a continuous infusion) to keep the plasma concentration at the desired steady-state (Css) within the therapeutic window. At steady state, rate of drug in = rate of drug out.

**Key formulas:** - Maintenance dose rate = (CL × target Css) / F - Per-dose amount = (CL × Css × τ) / F, where τ = dosing interval - For IV administration, F = 1. - Loading dose = (Vd × target Cp) / F

**Key determinants:** - **Clearance (CL)** is the main determinant of maintenance dose. Vd determines the loading dose, not the maintenance dose. - **Bioavailability (F):** oral doses must be increased to compensate for F < 1. - **Dosing interval (τ):** the same daily dose can be split into smaller, more frequent doses to reduce peak-trough fluctuation.

**Related pharmacokinetic principles:** - **Time to steady state** is about 4–5 half-lives. It depends only on t½, not on dose or dosing frequency. Changing the dose changes the Css level, not the time needed to reach it. - **Css** is proportional to dose rate and inversely proportional to CL. - **Half-life:** t½ = (0.7 × Vd) / CL. - A **loading dose** is used to reach the target concentration quickly when t½ is long (e.g., digoxin, amiodarone, lidocaine, phenytoin). It is not needed when the drug reaches steady state quickly.

**Clinical significance:** - **Renal impairment:** reduce the maintenance dose (or lengthen the interval) for renally cleared drugs, such as aminoglycosides, vancomycin, digoxin, lithium, and many β-lactams. The loading dose usually stays the same. - **Hepatic impairment or enzyme changes:** CYP inducers (rifampin, carbamazepine, phenytoin, chronic alcohol) increase CL, so a higher maintenance dose is needed. CYP inhibitors (cimetidine, ketoconazole, grapefruit juice, erythromycin) decrease CL, so a lower dose is needed. - **Zero-order (saturable) kinetics** (phenytoin, ethanol, high-dose aspirin) make dosing nonlinear. Small dose increases can cause disproportionately large rises in concentration and toxicity. - **Therapeutic drug monitoring** is used for narrow-therapeutic-index drugs (digoxin, lithium, aminoglycosides, vancomycin, phenytoin, warfarin via INR, theophylline). - **Heart failure, cirrhosis, and hypoalbuminemia** can change Vd, CL, or protein binding, which may change both loading and maintenance dosing.

**High-yield board pearls:** - Loading dose depends on Vd. Maintenance dose depends on CL. - Time to steady state depends on t½ (about 4–5 t½). - Renal failure → decrease the maintenance dose, not the loading dose. - Increasing the dose rate does not shorten the time to steady state. It only raises the Css. - Use a loading dose with a large Vd or long t½ when a rapid effect is needed.