How are paracetamol metabolize?
Paracetamol is metabolized primarily in the liver (Figure 1) by enzymes of phase I and II. Phase I reaction for paracetamol may occur by oxidation, reduction, and hydrolysis: It results in polar metabolites of the original chemicals and leads either to activation or inactivation of the drug.
Which enzyme is responsible for interpersonal differences in phase I paracetamol metabolism?
Phase I metabolism is predominantly mediated by CYP2E1 and produces a reactive metabolite.
What is the metabolite of paracetamol?
In adults, paracetamol is almost exclusively metabolized by the hepatic route and excreted into urine, with paracetamol glucuronide (47–62%) and paracetamol sulphate (25–36%) as the main metabolites.
Which p450s are involved in the metabolism of paracetamol?
These include the dose of paracetamol ingested, time to presentation, decreased liver glutathione, and induction of cytochrome P450 (CYP) isoenzymes responsible for the metabolism of paracetamol to its toxic metabolite N-acetyl-p-benzoquinoneimine (NAPQI).
Where is paracetamol metabolized?
Paracetamol is extensively metabolised (predominantly in the liver), the major metabolites being the sulphate and glucuronide conjugates.
What are the two main phases of drug metabolism?
Metabolism is often divided into two phases of biochemical reaction – phase 1 and phase 2. Some drugs may undergo just phase 1 or just phase 2 metabolism, but more often, the drug will undergo phase 1 and then phase 2 sequentially.
What are the factors affecting drug metabolism?
Physiological factors that can influence drug metabolism include age, individual variation (e.g., pharmacogenetics), enterohepatic circulation, nutrition, intestinal flora, or sex differences. In general, drugs are metabolized more slowly in fetal, neonatal and elderly humans and animals than in adults.
Is paracetamol hydrophobic or hydrophilic?
hydrophilic
The hydrophilic drugs paracetamol (PA) and theophylline (TP) and the lipophilic drugs griseofulvin (GF) and ketoconazole (KE) were used as model drugs.
Is acetaminophen metabolized in the kidneys?
Abstract. Acetaminophen (APAP) is normally metabolized in the liver and kidney by P450 enzymes. No toxicity is observed with therapeutic doses of APAP.
Where does Tylenol metabolize?
Acetaminophen is extensively metabolized by the liver via three main hepatic pathways: glucuronidation, sulfation, and CYP450 2E1 oxidation. Approximately 90% of acetaminophen is conjugated to sulfated and glucuronidated metabolites that are renally eliminated.
Does paracetamol go through first pass metabolism?
Paracetamol (acetaminophen) is a very common antipyretic and analgesic agent. It is well absorbed after oral administration, with bioavailability of 70–90% attributable to first pass metabolism [17,18,19].