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posted ago by Narg ago by Narg +141 / -0

https://makismd.substack.com/p/ivermectin-pharmacokinetics-how-ivermectin

Pharmacokinetic parameters of ivermectin following single doses were consistent with previous observations and with linear behavior up to single doses of 120 mg. Substantial variability in absorption was apparent across doses, but this phenomenon was attributable to absorption rates of < 50% in the fasted state and to the parallel panel design of the study.

Absorption of ivermectin was significantly higher when administered following a high-fat meal, approximately 2.5 times that in the fasted state. Although the effect of food on absorption of ivermectin had not been previously studied, this result was not unexpected. When the drug was administered in a hydroalcoholic solution, a similar increase in bioavailability was observed (compared to administration as a tablet). The extent of agreement between these results suggests that the poor solubility in water of the lipophilic ivermectin molecule limits absorption, but agents that help to solubilize the molecule (such as alcohol or bile) increase absorption of the drug. However, the standard high-fat meal is not representative of typical food ingestion. Furthermore, it is reassuring that despite a substantial increase in the AUC of ivermectin with administration of a high-fat meal, no toxicity was noted.

The apparent half-life for ivermectin identified in the product label is 16 hours or longer. The overall estimate from this study (approximately 18 h) is slightly longer. Half-life estimates varied somewhat with dose and means of administration from approximately 15 hours in fed subjects given 30 mg ivermectin doses to approximately 20 hours in the same group following administration of 30 mg ivermectin in the fasted state. Since the bioavailability is substantially higher when the drug is administered in the fed state, and a shorter half-life was observed in this state, it is possible that the half-life observed following oral administration is influenced by slow absorption of the drug, rather than being a true estimate of elimination half-life.

For those without Substack access, try the source link: https://www.researchgate.net/publication/11094854_Safety_Tolerability_and_Pharmacokinetics_of_Escalating_High_Doses_of_Ivermectin_in_Healthy_Adult_Subjects