Thursday, June 25, 2026
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Pharmacokinetics Calculator

Drug Clearance Calculator: CL from Dose/AUC, ke × Vd, and t½

Estimate systemic clearance from dose and AUC, from elimination rate constant and volume of distribution, or by deriving ke from half-life. Built for noncompartmental PK, maintenance dose planning, and renal or hepatic impairment study design — then verify against validated NCA and the drug label.

Quick Answer

Drug clearance (CL) is the volume of plasma cleared of drug per unit time — the primary parameter linking dose rate to exposure under linear PK. Estimate CL from dose and AUC (CL = F × Dose / AUC), from ke and Vd (CL = ke × Vd), or from half-life and Vd. Pharma teams use clearance for maintenance dose planning, renal/hepatic impairment study design, and noncompartmental analysis alongside the Maintenance Dose, AUC, and Bioavailability calculators on this PK hub.

Clearance Formula Options
CL = F × Dose / AUC   |   CL = ke × Vd   |   ke = 0.693 / t1/2
Dose = mg; AUC = mg*h/L; F = bioavailability fraction; ke = 1/h; Vd = L; t1/2 = hours.

Calculate Drug Clearance

Select a mode based on available pharmacokinetic data: dose and AUC, ke and Vd, or half-life and Vd.

Dose and exposure

Leave blank or set to 100% for IV dosing.

Estimated Clearance

- L/h

Select a mode and calculate to see results.

Clearance
-
mL/min
Weight-normalized
-
L/h/kg
Weight-normalized
-
mL/min/kg
Derived ke
-
1/h, if applicable

How to Use This Clearance Calculator

1
Dose / AUC: Enter dose in mg and AUC in mg*h/L. For IV dosing, leave F blank or set it to 100%. For oral or other non-IV routes, enter bioavailability as a percent.
2
ke × Vd: Enter the elimination rate constant in 1/h and volume of distribution in L. The calculator reports CL = ke × Vd.
3
Half-life + Vd: Enter half-life in hours and Vd in L. The calculator derives ke as 0.693 / t1/2 and then calculates CL.
4
Optionally add body weight in kg to display clearance normalized as L/h/kg and mL/min/kg.

Clearance, AUC, and Maintenance Dosing

Clearance is the pharmacokinetic term that links exposure to dose rate. With linear pharmacokinetics, higher clearance produces lower exposure for the same dose, while lower clearance produces higher AUC and greater accumulation risk.

Dose-rate relationship

At steady state, average concentration is proportional to dose rate divided by clearance. Rearranged for dosing: maintenance dose rate = target average concentration × CL / F.

Because AUC is inversely related to clearance, reduced renal or hepatic function often raises exposure unless the dose, interval, or route is adjusted. For narrow therapeutic index drugs, measured concentrations and validated population PK models are usually more reliable than simple equations alone.

Renal and Hepatic Clearance

Total clearance may include renal clearance, hepatic metabolism, biliary clearance, and other routes. Renal impairment can reduce filtration or secretion for renally eliminated drugs. Hepatic impairment can reduce metabolic capacity, hepatic blood flow extraction, or biliary elimination for hepatically cleared drugs.

Organ-specific effects depend on the drug. A low-extraction hepatically metabolized drug may be sensitive to intrinsic enzyme capacity and protein binding, while a high-extraction drug may be more sensitive to hepatic blood flow. Always interpret calculated CL with route, assay, matrix, sampling design, and organ function context.

Linear Pharmacokinetic Caveats

These calculations assume first-order elimination and linear exposure. They may not apply when clearance changes over time, metabolism is saturable, distribution is multicompartmental, protein binding is concentration-dependent, dialysis is present, or biologics show target-mediated drug disposition.

For non-IV dosing, remember that CL = F × Dose / AUC requires a known bioavailability. If F is unknown, Dose/AUC is apparent clearance (CL/F), not true systemic clearance.

Pharma & clinical trial context

Clearance is a primary output of Phase 1 pharmacokinetic studies, population PK analyses, and renal or hepatic impairment cohort designs. Sponsors report CL from dose-normalized AUC in CSR tables, use CL to justify maintenance dose selection, and compare CL across special populations against healthy volunteers per FDA renal and hepatic PK guidance.

This calculator integrates with the NovaPharmaNews PK hub: quantify exposure with the AUC Calculator; estimate route-specific F with the Bioavailability Calculator; plan steady-state dosing with the Maintenance Dose Calculator; relate t½ to CL and Vd with the Half-Life Calculator; and bridge loading to maintenance regimens with the Loading Dose Calculator.

Protocol appendices should document whether clearance is model-dependent (ke × Vd) or noncompartmental (F × Dose / AUC), the AUC method (AUC0–t vs AUC0–∞), matrix and sampling schedule, and whether reported values are CL or CL/F. For bioequivalence and formulation studies, clearance estimates support exposure comparisons but do not replace validated NCA software and regulatory submission workflows.

Evidence & sources

Frequently Asked Questions

Drug clearance is the apparent volume of plasma or blood from which a drug is completely removed per unit time. It is commonly reported as L/h or mL/min and reflects the combined effect of renal excretion, hepatic metabolism, biliary elimination, and other elimination pathways. Clearance is the central PK parameter that connects dose rate to average steady-state concentration under linear pharmacokinetics.
For intravenous dosing with complete bioavailability, systemic clearance equals dose divided by area under the curve: CL = Dose / AUC, where dose is in mg and AUC is in mg·h/L. This is the noncompartmental clearance estimate from total exposure after a single IV dose. Use the AUC Calculator to derive AUC from concentration–time data before applying this relationship.
For non-IV routes, only the fraction reaching systemic circulation contributes to exposure: CL = F × Dose / AUC, where F is bioavailability as a fraction. If F is 50%, half the administered dose reaches the systemic circulation, so the same AUC implies lower true clearance than Dose/AUC alone would suggest. Use the Bioavailability Calculator when comparing routes or estimating F from PK study data.
When oral or extravascular bioavailability is unknown, dividing dose by AUC yields apparent clearance (CL/F), not true systemic clearance. CL/F is useful for comparing exposure across doses or cohorts on the same route, but it cannot be used directly in maintenance dose equations that require true CL unless F is known or assumed. Always document whether reported clearance is CL or CL/F in protocol appendices and CSR tables.
CL = ke × Vd is a model-dependent estimate from compartmental PK parameters (elimination rate constant and volume of distribution from the same model). Noncompartmental clearance CL = F × Dose / AUC is model-independent and derived directly from dose and total exposure. Both should agree when the same linear one-compartment assumptions hold; they may diverge for multicompartment drugs, saturable elimination, or when ke and Vd come from different analysis methods.
CL = ke × Vd applies when ke and Vd describe the same first-order, linear pharmacokinetic model — typically one-compartment analysis or terminal-phase parameters from model fitting. This calculator also derives ke from half-life (ke = 0.693 / t½) before applying CL = ke × Vd. Use the Half-Life Calculator and Volume of Distribution Calculator to obtain consistent inputs from trial or literature data.
Renal clearance reflects drug elimination through glomerular filtration, tubular secretion, and reabsorption in the kidney. Hepatic clearance reflects metabolism, biliary excretion, and hepatic blood flow extraction in the liver. Total clearance is often the sum of independent organ clearances (CLtotal ≈ CLrenal + CLhepatic + other routes). Renal or hepatic impairment studies measure how CL changes and inform dose adjustment per FDA renal and hepatic PK guidance.
At steady state under linear PK, average concentration equals dose rate divided by clearance: Css = (F × dose rate) / CL, rearranged as maintenance dose rate = Css × CL / F. Higher clearance lowers exposure for the same dose; lower clearance raises AUC and accumulation risk. Use the Maintenance Dose Calculator to plan ongoing dosing after estimating CL from this tool or from dose/AUC data.
A typical PK workflow: derive AUC from concentration–time profiles with the AUC Calculator; estimate CL as F × Dose / AUC here; quantify route-specific F with the Bioavailability Calculator; then plan steady-state dosing with the Maintenance Dose Calculator. Loading doses depend on Vd, not CL directly — use the Loading Dose Calculator when rapid target concentration is needed before maintenance dosing driven by clearance.
These equations assume first-order elimination, stable clearance over the dosing interval, dose-proportional exposure, and consistent units. They may not apply when clearance changes over time, metabolism is saturable, distribution is multicompartmental, protein binding is concentration-dependent, dialysis is present, or sampling does not capture the full AUC. Always interpret calculated CL with route, matrix, sampling design, and organ function context.
Biologics may show target-mediated drug disposition (TMDD), where clearance decreases as target sites saturate — violating the constant-CL assumption. Drugs with saturable metabolism (e.g., phenytoin, alcohol at high doses) follow zero-order or mixed kinetics where CL is not constant. High hepatic extraction drugs may be flow-limited rather than capacity-limited. For these agents, population PK modeling and therapeutic drug monitoring usually replace simple clearance equations.
No. This tool supports educational clearance estimates from summary PK parameters. Full noncompartmental analysis (NCA) requires validated software, complete concentration–time datasets, AUC extrapolation rules, and regulatory documentation per ICH and FDA bioanalytical guidance. Platforms such as MetricGate offer upload-based NCA suites for study reporting. Use this calculator for quick estimates, protocol drafts, and PK hub cross-checks — not as a substitute for validated NCA workflows or prescribing decisions.

Related Calculators

AUC AUC Calculator MD Maintenance Dose Calculator F Bioavailability Calculator t½ Half-Life Calculator LD Loading Dose Calculator

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