A Large Impact of Obesity on the Disposition of Ivermectin, Moxidectin and Eprinomectin in a Canine Model: Relevance for COVID-19 Patients

Abstract

Ivermectin (IVM) and moxidectin (MOX) are used extensively as parasiticides in veterinary medicine. Based on in vitro data, IVM has recently been proposed for the prevention and treatment of COVID-19 infection, a condition for which obesity is a major risk factor. In patients, IVM dosage is based on total body weight and there are no recommendations to adjust dosage in obese patients. The objective of this study was to establish, in a canine model, the influence of obesity on the clearance and steady-state volume of distribution of IVM, MOX, and a third analog, eprinomectin (EPR). An experimental model of obesity in dogs was based on a high calorie diet. IVM, MOX, and EPR were administered intravenously, in combination, to a single group of dogs in two circumstances, during a control period and when body weight had been increased by 50%. In obese dogs, clearance, expressed in absolute values (L/day), was not modified for MOX but was reduced for IVM and EPR, compared to the initial control state. However, when scaled by body weight (L/day/kg), plasma clearance was reduced by 55, 42, and 63%, for IVM, MOX and EPR, respectively. In contrast, the steady-state volume of distribution was markedly increased, in absolute values (L), by obesity. For IVM and MOX, this obese dog model suggests that the maintenance doses in the obese subject should be based on lean body weight rather than total weight. On the other hand, the loading dose, when required, should be based on the total body weight of the obese subject.

Inter-coat protein loading of active ingredients into Tobacco mild green mosaic virus through partial dissociation and reassembly of the virion

“…IVM and FLP had the highest logP values of 4.4 and 3.33, respectively. CTD and RIF had values of 1.3 and 2.4, respectively 50 – 52 . The values for IVM and FLP indicate the molecules are water insoluble, which matches well to our observations in the loading experiments.…”

Bayesian estimation in veterinary pharmacology: A conceptual and practical introduction

“…External predictions of the concentration-time relationships, corresponding to subjects or conditions not contained within the data, are another important application of pharmacokinetic mod- from the information at hand, then we must simultaneously take into account our uncertainty about relevant pharmacokinetic parameters in goats, including between-subject variation, and our uncertainty about pharmacokinetic parameters in sheep (Hartnack & Roos, 2021). For frequentist approaches this may be an intractable problem, making direct quantification of uncertainty difficult for secondary parameters or functions thereof, for example, in Bousquet-Mélou et al (2021).…”

“…For frequentist approaches this may be an intractable problem, making direct quantification of uncertainty difficult for secondary parameters or functions thereof, for example, in Bousquet‐Mélou et al. (2021).…”