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The toxic dose of paracetamol is highly variable. In general the recommended maximum daily dose for healthy adults is 4 grams. [17] [18] Higher doses lead to increasing risk of toxicity. In adults, single doses above 10 grams or 200 mg/kg of bodyweight, whichever is lower, have a reasonable likelihood of causing toxicity.
For comparison, those with a V d L/kg body weight of less than 0.2 are mainly distributed in blood plasma, 0.2-0.7 mostly in the extracellular fluid and those with more than 0.7 are distributed throughout total body water.
The median lethal dose of a substance is defined as the dose that leads to death in 50% of the tested population. It is a significant parameter in toxicology study and indicates the acute toxicity of a particular substance. LD50 is usually expressed in the weight of the chemical administered in milligram per unit of body weight (mg/kg). [29]
Paracetamol's bioavailability is dose-dependent: it increases from 63 % for 500 mg dose to 89 % for 1000 mg dose. [6] Its plasma terminal elimination half-life is 1.9–2.5 hours, [ 6 ] and volume of distribution is roughly 50 L. [ 132 ] Protein binding is negligible, except under the conditions of overdose, when it may reach 15–21 %. [ 6 ]
The therapeutic index (TI; also referred to as therapeutic ratio) is a quantitative measurement of the relative safety of a drug with regard to risk of overdose.It is a comparison of the amount of a therapeutic agent that causes toxicity to the amount that causes the therapeutic effect. [1]
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The minimum dosage at which paracetamol causes toxicity usually is 7.5 to 10g in the average person. [2] The lethal dose is usually between 10 g and 15 g. [citation needed] Concurrent alcohol intake lowers these thresholds significantly. Chronic alcoholics may be more susceptible to adverse effects due to reduced glutathione levels. [3]