Sildenafil pharmacokinetics describes how the drug moves through the body after administration. After oral dosing, sildenafil is rapidly absorbed, reaches systemic circulation with mean absolute bioavailability of about 41%, distributes extensively into tissues, undergoes predominantly CYP-mediated hepatic metabolism and is eliminated mainly as metabolites.
Several quantitative parameters summarize that pathway. In the fasted state, maximum plasma concentrations are reached within 30 to 120 minutes with a median Tmax of about 60 minutes. The mean steady-state volume of distribution is approximately 105 L, sildenafil is about 96% protein bound, and parent sildenafil has a terminal half-life of about 4 hours.
This page is the master sildenafil PK hub. It provides the numeric framework connecting absorption, bioavailability, Tmax, Cmax, AUC, distribution, metabolism, clearance and half-life while reserving metric-specific interpretation and subgroup detail for the dedicated PK pages.
The sildenafil concentration-time profile reflects several processes operating simultaneously rather than a simple sequence in which one stage completely ends before another starts. Absorption raises systemic concentrations while distribution, metabolism and elimination are already occurring.
Current U.S. labeling provides several useful reference values for oral sildenafil: mean absolute bioavailability is approximately 41%, fasted Tmax is 30 to 120 minutes with a median of about 60 minutes, mean steady-state volume of distribution is approximately 105 L and terminal half-life is about 4 hours.
These values describe different parts of the PK system. No single parameter can substitute for the full concentration-time profile, which is why the dedicated sildenafil concentration-time page interprets how the measurements fit together.
| PK Feature | Sildenafil Reference Value | Primary Meaning |
|---|---|---|
| Absolute oral bioavailability | Mean approximately 41% (reported range 25–63%) | Fraction of oral dose reaching systemic circulation unchanged |
| Fasted Tmax | 30–120 minutes; median approximately 60 minutes | Timing of the observed concentration peak |
| High-fat meal effect | Mean Tmax delay approximately 60 minutes; Cmax reduction approximately 29% | Reduced rate of oral absorption |
| Steady-state volume of distribution | Approximately 105 L | Indicates distribution beyond the plasma compartment |
| Plasma protein binding | Approximately 96% for parent and major active metabolite | Most circulating drug is protein bound |
| Major metabolism | CYP3A major; CYP2C9 minor | Principal hepatic biotransformation pathways |
| Terminal half-life | About 4 hours for parent and active metabolite | Terminal concentration-decline time scale |
| Excretion of drug-related material | Approximately 80% feces and 13% urine after an oral dose | Predominantly metabolites rather than unchanged parent drug |
Sildenafil is rapidly absorbed after oral administration. In the fasted state, observed plasma concentrations typically reach their maximum within 30 to 120 minutes, with a median Tmax of approximately 60 minutes.
Absorption governs the rising portion of the oral concentration-time curve, but Tmax does not measure absorption alone because distribution and elimination are occurring while drug is still entering the circulation.
Food provides a clear example of altered absorption rate: a high-fat meal delays mean Tmax by about 60 minutes and reduces mean Cmax by approximately 29%. The sildenafil absorption page covers the pre-systemic uptake process, while meal-specific interpretation belongs on the sildenafil food effects page.
| Absorption Feature | Observed Sildenafil Finding |
|---|---|
| Oral absorption | Rapid |
| Fasted Tmax range | 30–120 minutes |
| Median fasted Tmax | Approximately 60 minutes |
| High-fat meal effect on Tmax | Mean delay of approximately 60 minutes |
| High-fat meal effect on Cmax | Mean reduction of approximately 29% |
| Detailed absorption resource | Sildenafil Absorption |
Mean absolute oral sildenafil bioavailability is approximately 41%, with a reported range of 25% to 63%. This does not mean that only 41% of an oral dose enters the gastrointestinal wall.
Absolute bioavailability reflects the net amount of unchanged sildenafil reaching systemic circulation after both gastrointestinal uptake and presystemic loss. Substantial first-pass metabolism contributes to the difference between absorbed drug and unchanged systemic drug.
Bioavailability is therefore an input parameter within the larger exposure system. AUC is used in its quantitative determination but is not synonymous with bioavailability. Detailed interpretation is covered on the sildenafil bioavailability page.
| Concept | Sildenafil PK Context |
|---|---|
| Absolute oral bioavailability | Mean approximately 41% |
| Reported range | Approximately 25–63% |
| GI absorption | Precedes systemic availability |
| Presystemic metabolism | Reduces unchanged drug reaching systemic circulation |
| Bioavailability vs absorption | Related but not equivalent concepts |
| Dedicated resource | Sildenafil Bioavailability |
After oral administration, sildenafil plasma concentrations rise as systemic input exceeds removal. The concentration curve eventually reaches Cmax at Tmax and then declines as drug input falls relative to distribution and elimination.
Tmax answers when the observed peak occurs; Cmax answers how high that peak is. Neither parameter alone represents total systemic exposure, and neither should be used as a direct measure of pharmacodynamic effect.
Sildenafil pharmacokinetics is dose-proportional over the recommended oral dose range, meaning AUC and Cmax generally increase with dose under the studied conditions. Detailed interpretation remains on the sildenafil Tmax, sildenafil Cmax and dose proportionality pages.
| Metric | What It Represents | Sildenafil Context |
|---|---|---|
| Tmax | Time of observed peak concentration | 30–120 minutes fasted; median about 60 minutes |
| Cmax | Maximum observed plasma concentration | Peak magnitude; study- and dose-dependent |
| AUC | Integrated exposure over time | Changes with systemic input and clearance |
| Dose proportionality | Relationship of dose to exposure | Sildenafil exposure is dose-proportional over the recommended range |
After entering systemic circulation, sildenafil distributes beyond plasma into tissues. Current labeling reports a mean steady-state volume of distribution of approximately 105 L, indicating distribution beyond the vascular compartment.
Parent sildenafil and its major circulating N-desmethyl metabolite are each approximately 96% bound to plasma proteins. Labeling states that this protein binding is independent of total drug concentration over the relevant studied range.
Distribution helps determine the relationship between the amount of drug in the body and the concentration measured in plasma. It also contributes to interpretation of terminal decline and half-life. The sildenafil distribution page treats these concepts in detail.
| Distribution Parameter | Sildenafil Finding |
|---|---|
| Mean Vss | Approximately 105 L |
| Parent sildenafil protein binding | Approximately 96% |
| N-desmethyl metabolite protein binding | Approximately 96% |
| Protein binding vs total concentration | Reported as concentration-independent |
| Interpretation | Sildenafil distributes beyond plasma into tissues |
| Dedicated resource | Sildenafil Distribution |
Sildenafil is cleared predominantly through hepatic microsomal metabolism. Current labeling identifies CYP3A as the major metabolic route and CYP2C9 as a minor route.
The major circulating active metabolite is formed through N-desmethylation. It has a PDE selectivity profile similar to parent sildenafil and approximately 50% of the parent's in-vitro PDE5 potency.
In healthy volunteers, metabolite plasma concentrations are approximately 40% of parent concentrations, leading labeling to estimate an approximately 20% contribution to overall sildenafil pharmacological effects. The metabolite is then further metabolized.
Detailed reaction pathways belong on the sildenafil metabolism page, CYP-specific interaction effects on the CYP3A4 page, and metabolite PK on the active metabolite page.
| Metabolic Feature | Sildenafil Finding |
|---|---|
| Major enzyme pathway | CYP3A |
| Minor enzyme pathway | CYP2C9 |
| Major active metabolite | N-desmethyl sildenafil |
| Metabolite in-vitro PDE5 potency | Approximately 50% of parent |
| Metabolite plasma concentration | Approximately 40% of parent in healthy volunteers |
| Estimated pharmacologic contribution | Approximately 20% |
Sildenafil parent drug disappears from plasma mainly through metabolic clearance rather than extensive renal excretion of unchanged drug. The resulting metabolites are then eliminated from the body.
After oral or intravenous sildenafil, drug-related material is excreted as metabolites predominantly in feces. Current labeling reports approximately 80% of the administered oral dose recovered through feces and approximately 13% through urine.
Both parent sildenafil and the major active metabolite have terminal half-lives of about 4 hours. Half-life describes terminal concentration decline and should not be interpreted as the duration of clinical effect.
The distinction between removal efficiency and terminal decline is treated on the sildenafil clearance page and sildenafil half-life page.
| Elimination Feature | Sildenafil Finding |
|---|---|
| Primary parent-drug removal mechanism | Metabolic clearance |
| Fecal recovery | Approximately 80% of administered oral dose as metabolites |
| Urinary recovery | Approximately 13% of administered oral dose as metabolites |
| Parent terminal half-life | About 4 hours |
| Active-metabolite terminal half-life | About 4 hours |
| Half-life vs clinical duration | Not equivalent |
AUC integrates sildenafil concentration across time and is therefore the central measure of total systemic exposure. It complements Cmax, which describes the peak, and Tmax, which describes peak timing.
For oral dosing, exposure depends on both the fraction of dose entering systemic circulation and the efficiency of removal. A change in bioavailability can alter AUC by changing systemic input, while a change in clearance can alter AUC by changing drug removal.
This distinction is important when interpreting interactions or organ-function effects: an increase in AUC describes greater integrated exposure but does not by itself identify the mechanism responsible for that increase.
Metric-specific calculation belongs on the sildenafil AUC page, while sildenafil exposure integrates AUC with Cmax and variability.
| Exposure Measure | Primary Information | What It Does Not Mean |
|---|---|---|
| Cmax | Peak concentration | Total exposure |
| Tmax | Peak timing | Clinical onset |
| AUC | Integrated systemic exposure | A direct measurement of metabolism |
| Bioavailability | Fraction reaching systemic circulation unchanged | AUC itself |
| Clearance | Efficiency of systemic removal | Half-life itself |
The sildenafil concentration-time curve combines systemic input and removal. During the early phase after oral administration, absorption raises concentration while distribution, metabolism and elimination simultaneously oppose that increase.
At Cmax, net concentration rise has stopped, but this does not mean absorption has instantaneously ended or that pharmacodynamic effect has reached a universal maximum. After the peak, concentrations decline as systemic input becomes smaller than distribution and elimination processes.
The terminal portion of the curve is used to characterize terminal half-life, while the entire area beneath the curve contributes to AUC. These regions answer different PK questions and should not be collapsed into a single idea of how long sildenafil 'stays in the body.'
The sildenafil concentration-time page provides the full curve-reading framework.
| Curve Region / Metric | Primary Interpretation |
|---|---|
| Rising phase | Net systemic input exceeds removal |
| Tmax | Time of observed concentration peak |
| Cmax | Magnitude of observed concentration peak |
| Post-peak decline | Removal increasingly exceeds ongoing input |
| Terminal phase | Late concentration decline used for terminal half-life interpretation |
| AUC | Area integrating concentration across the measured time interval |
Sildenafil PK varies because absorption conditions, metabolic capacity, age, organ function and interacting drugs can change one or more parts of the concentration-time profile.
Current labeling provides useful examples. Healthy volunteers aged 65 years or older had approximately 84% higher total sildenafil AUC than younger volunteers, although the increase in free sildenafil AUC was smaller at approximately 45%.
In severe renal impairment with creatinine clearance below 30 mL/min, sildenafil AUC and Cmax were approximately doubled. In Child-Pugh A or B hepatic impairment, AUC was approximately 85% higher and Cmax approximately 47% higher. These are population PK findings, not dose-conversion formulas.
Detailed interpretation remains on the PK variability page, renal impairment PK page and hepatic impairment PK page.
| Source of Variability | Observed Sildenafil PK Effect |
|---|---|
| High-fat meal | Mean Tmax +~60 minutes; Cmax -~29% |
| Age ≥65 years | Total sildenafil AUC approximately +84%; free AUC approximately +45% |
| Severe renal impairment | Parent sildenafil AUC and Cmax approximately doubled |
| Child-Pugh A/B hepatic impairment | AUC approximately +85%; Cmax approximately +47% |
| CYP3A inhibition / induction | Can increase or decrease sildenafil exposure through altered metabolism |
Pharmacokinetics describes sildenafil exposure over time; pharmacodynamics describes how sildenafil interacts with targets and produces biological responses. The two domains are connected but cannot be substituted for one another.
For example, fasted median Tmax is about 60 minutes, but that does not mean clinical onset is fixed at 60 minutes. Likewise, an approximately 4-hour terminal half-life does not mean the clinical response begins or ends at a four-hour boundary.
PK provides the exposure available for PDE5 inhibition. PD determines how that exposure interacts with the NO–cGMP system and tissue physiology. The sildenafil pharmacodynamics page covers that response side, while how sildenafil works provides the nontechnical mechanism overview.
| Domain | Primary Question | Sildenafil Measures / Examples |
|---|---|---|
| Pharmacokinetics | How does sildenafil exposure change over time? | Bioavailability, Tmax, Cmax, AUC, Vss, clearance, half-life |
| Pharmacodynamics | What does sildenafil exposure do biologically? | PDE5 inhibition, cGMP signaling and measured physiological response |
| PK-PD relationship | How does exposure connect to response? | Concentration-effect and effect-time relationships |
| Key boundary | Does a PK metric directly equal a clinical effect? | No |
Current U.S. labeling reports mean absolute oral bioavailability of about 41%, fasted Tmax of 30 to 120 minutes with a median of about 60 minutes, mean steady-state volume of distribution of about 105 L, approximately 96% plasma protein binding and a terminal half-life of about 4 hours.
Sildenafil is metabolized predominantly by CYP3A, with CYP2C9 providing a minor pathway. N-demethylation produces the major circulating active metabolite, which is then further metabolized.
Parent sildenafil is removed predominantly through metabolism. Drug-related material is excreted mainly as metabolites, with approximately 80% of an administered oral dose recovered in feces and approximately 13% in urine.
Yes. Current labeling reports that a high-fat meal delays mean Tmax by about 60 minutes and lowers mean Cmax by about 29%, demonstrating a slower rate of absorption.
Exposure can vary because of factors including food, age, metabolic-enzyme activity and organ function. Current labeling reports higher exposure in older adults, severe renal impairment and mild-to-moderate hepatic impairment.
No. The approximately 4-hour terminal half-life describes the late plasma concentration decline. Clinical onset and duration are pharmacodynamic concepts and should not be inferred directly from half-life.