Paracetamol Stats & Data
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DrugBankDescription
Acetaminophen (paracetamol), also commonly known as _Tylenol_, is the most commonly taken analgesic worldwide and is recommended as first-line therapy in pain conditions by the World Health Organization (WHO). It is also used for its antipyretic effects, helping to reduce fever. This drug was initially approved by the U.S. FDA in 1951 and is available in a variety of forms including syrup form, regular tablets, effervescent tablets, injection, suppository, and other forms. Acetaminophen is often found combined with other drugs in more than 600 over the counter (OTC) allergy medications, cold medications, sleep medications, pain relievers, and other products. Confusion about dosing of this drug may be caused by the availability of different formulas, strengths, and dosage instructions for children of different ages. Due to the possibility of fatal overdose and liver failure associated with the incorrect use of acetaminophen, it is important to follow current and available national and manufacturer dosing guidelines while this drug is taken or prescribed.
Mechanism of Action
According to its FDA labeling, acetaminophen's exact mechanism of action has not been fully established - despite this, it is often categorized alongside NSAIDs (nonsteroidal anti-inflammatory drugs) due to its ability to inhibit the cyclooxygenase (COX) pathways. It is thought to exert central actions which ultimately lead to the alleviation of pain symptoms. One theory is that acetaminophen increases the pain threshold by inhibiting two isoforms of cyclooxygenase, COX-1 and COX-2, which are involved in prostaglandin (PG) synthesis. Prostaglandins are responsible for eliciting pain sensations. Acetaminophen does not inhibit cyclooxygenase in peripheral tissues and, therefore, has no peripheral anti-inflammatory effects. Though acetylsalicylic acid (aspirin) is an irreversible inhibitor of COX and directly blocks the active site of this enzyme, studies have shown that acetaminophen (paracetamol) blocks COX indirectly. Studies also suggest that acetaminophen selectively blocks a variant type of the COX enzyme that is unique from the known variants COX-1 and COX-2. This enzyme has been referred to as _COX-3_. The antipyretic actions of acetaminophen are likely attributed to direct action on heat-regulating centers in the brain, resulting in peripheral vasodilation, sweating, and loss of body heat.
Pharmacodynamics
Animal and clinical studies have determined that acetaminophen has both antipyretic and analgesic effects. This drug has been shown to lack anti-inflammatory effects. As opposed to the _salicylate_ drug class, acetaminophen does not disrupt tubular secretion of uric acid and does not affect acid-base balance if taken at the recommended doses. Acetaminophen does not disrupt hemostasis and does not have inhibitory activities against platelet aggregation. Allergic reactions are rare occurrences following acetaminophen use.
Metabolism
Acetaminophen is the major metabolite of _phenacetin_ and _acetanilid_. Acetaminophen is mainly metabolized in the liver by first-order kinetics and its metabolism of comprised of 3 pathways: conjugation with glucuronide, conjugation with sulfate, and oxidation through the cytochrome P450 enzyme pathway, mainly CYP2E1, to produce a reactive metabolite (N-acetyl-p-benzoquinone imine or NAPQI). At normal therapeutic doses, NAPQI undergoes fast conjugation with glutathione and is subsequently metabolized to produce both cysteine and mercapturic acid conjugates. High doses of acetaminophen (overdoses) can lead to hepatic necrosis due to the depletion of glutathione and of binding of high levels of reactive metabolite (NAPQI) to important parts of liver cells. The abovementioned damage to the liver can be prevented by the early administration of sulfhydryl compounds, for example, methionine and N-acetylcysteine.
Absorption
Acetaminophen has 88% oral bioavailability and reaches its highest plasma concentration 90 minutes after ingestion. Peak blood levels of free acetaminophen are not reached until 3 hours after rectal administration of the suppository form of acetaminophen and the peak blood concentration is approximately 50% of the observed concentration after the ingestion of an equivalent oral dose (10-20 mcg/mL). The percentage of a systemically absorbed rectal dose of acetaminophen is inconsistent, demonstrated by major differences in the bioavailability of acetaminophen after a dose administered rectally. Higher rectal doses or an increased frequency of administration may be used to attain blood concentrations of acetaminophen similar to those attained after oral acetaminophen administration.
Indication
In general, acetaminophen is used for the treatment of mild to moderate pain and reduction of fever. It is available over the counter in various forms, the most common being oral forms. Acetaminophen _injection_ is indicated for the management of mild to moderate pain, the management of moderate to severe pain with adjunctive opioid analgesics, and the reduction of fever. Because of its low risk of causing allergic reactions, this drug can be administered in patients who are intolerant to salicylates and those with allergic tendencies, including bronchial asthmatics. Specific dosing guidelines should be followed when administering acetaminophen to children.
Half-life
The half-life for adults is 2.5 h after an intravenous dose of 15 mg/kg. After an overdose, the half-life can range from 4 to 8 hours depending on the severity of injury to the liver, as it heavily metabolizes acetaminophen.
Protein Binding
The binding of acetaminophen to plasma proteins is low (ranging from 10% to 25%), when given at therapeutic doses.
Elimination
Acetaminophen metabolites are mainly excreted in the urine. Less than 5% is excreted in the urine as free (unconjugated) acetaminophen and at least 90% of the administered dose is excreted within 24 hours.
Volume of Distribution
Volume of distribution is about 0.9L/kg. 10 to 20% of the drug is bound to red blood cells. Acetaminophen appears to be widely distributed throughout most body tissues except in fat.
Clearance
Adults: 0.27 L/h/kg following a 15 mg/kg intravenous (IV) dose. Children: 0.34 L/h/kg following a 15 mg/kg intravenous (IV dose).
Measured Affinities
Guide to PHARMACOLOGYMeasured binding and functional data for paracetamol, curated by the IUPHAR/BPS Guide to PHARMACOLOGY. Each row cites the paper it came from. Lower concentrations mean tighter binding — a value in the sub-nanomolar range indicates a very potent interaction.
| Target | Action | Measure | Value | Concentration | Species | Source |
|---|---|---|---|---|---|---|
| TRPV4 TRPV4 | Inhibition | pIC50 | 6.52 | 302 nM | Human | PMID 32051870 |
| COX-2 PTGS2 | Inhibition | pKi | 4.59 | 25,704 nM | Human | PMID 17884974 |
| COX-1 PTGS1 | Inhibition | pKi | 3.94 | 114,815 nM | Human | PMID 17884974 |
Reading this. pKi, pEC50 and pIC50 are negative log molar values, so a higher number means a tighter interaction; the concentration column converts them for you. Values from non-human species are laboratory measurements and do not translate directly to human effect. Receptor affinity is not a dose — it describes what a molecule binds, not how much of it is safe to take.
Receptor data from the IUPHAR/BPS Guide to PHARMACOLOGY (v2026.2), licensed CC BY-SA 4.0. Matched to this substance by InChIKey.
Nausea, vomiting, and abdominal pain usually occur within 2-3 hours after ingestion of toxic doses of the drug. In severe poisoning, CNS stimulation, excitement, and delirium may occur initially. Each year, approximately 500 fatalities and 50,000 emergency department admissions in the United States are linked to acetaminophen. In 2021, US poison control centers recorded over 80,000 cases. Under normal circumstances, NAPQI is neutralized by glutathione to form nontoxic metabolites. However, in the case of excessive doses of acetaminophen, the normal phase II drug metabolism pathways become depleted.
LD50
LD50: 338 mg/kg (Oral, Mouse) (A308)LD50: 1944 mg/kg (Oral, Rat) (A308)
Carcinogenicity
Group 3: Not classifiable as to its carcinogenicity to humans
Liver injury risk
High concern (frequent serious cases reported)
Health effects (PubChem excerpts)
Skin rashes, blood disorders and a swollen pancreas have occasionally happened in people taking the drug on a regular basis for a long time.
Tolerance & Pharmacokinetics
drugs.wikiTolerance Decay
Experience Report Analysis
ErowidDemographics
Gender Distribution
Age Distribution
Reports Over Time
Dosage Distribution
Dose distribution from experience reports, one dose per report (the first listed). Doses above Q3 + 3×IQR, far above what people typically take, are left out of the median and range and listed under each route: most are real heavy doses or overdoses, not mistakes.
1 report gave a dose above the typical range (2,400 mg), so it is not in the figures above. Listing a dose here does not mean it is safe.
Show the report
- 2,400 mg · another drug taken too
Real-World Dose Distribution
ErowidFrom 307 of 324 recorded dose entries: those that state a weight (mg, g or µg), in routes with at least five of them. Values above Q3 + 3×IQR, far above what people typically take, are left out; they can include real heavy doses and overdoses, not only mistakes.
Oral (n=288)
Insufflated (n=11)
Common Combinations
Most co-occurring substances, as a share of all 32 reports filed under Paracetamol; whiskers are 95% intervals
Form / Preparation
Most common forms and preparations, as a share of the 13 reports that give one
Too few reports for bars: these forms come from 13 reports, and a bar is drawn only from 20 reports or more. With fewer, a percentage cannot tell a common effect from a rare one. Counts are shown instead. Why 20?
- Pill / Tablet 12 of 13
Body-Weight Dosing
Dose per kg of body weight, one dose per report (the first listed), from reports giving a weight of 30–250 kg. Doses above Q3 + 3×IQR, far above what people typically take, are left out of the median and range and listed under each route.
1 report gave a dose above the typical range (42.328 mg/kg), so it is not in the figures above. Listing a dose here does not mean it is safe.
Show the report
- 42.328 mg/kg · another drug taken too
Redose Patterns
Redosing behavior across 19 reports
Too few reports for a chart: redosing is known from 19 reports, and a split is drawn only from 20 reports or more. Counts are shown instead. Why 20?
- Single dose 13 of 19
- Redosed 6 of 19