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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.
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 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]
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]
In toxicology, the median lethal dose, LD 50 (abbreviation for "lethal dose, 50%"), LC 50 (lethal concentration, 50%) or LCt 50 is a toxic unit that measures the lethal dose of a given substance. [1] The value of LD 50 for a substance is the dose required to kill half the members of a tested population after a specified test duration.
The lowest lethal dose (LD Lo) is the least amount of drug that can produce death in a given animal species under controlled conditions. [ 6 ] [ 7 ] The dosage is given per unit of bodyweight (typically stated in milligrams per kilogram ) of a substance known to have resulted in fatality in a particular species.
The area under the effect curve (AUEC) is an integral of the effect of a drug over time, estimated as a previously-established function of concentration. It was proposed to be used instead of AUC in animal-to-human dose translation, as computer simulation shows that it could cope better with half-life and dosing schedule variations than AUC.
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