A Large Impact of Obesity on the Disposition of Ivermectin, Moxidectin and Eprinomectin in a Canine Model: Relevance for COVID-19 Patients
Bousquet-Mélou et al.
, A Large Impact of Obesity on the Disposition of Ivermectin, Moxidectin and Eprinomectin in a Canine Model:..
, Frontiers in Pharmacology, doi:10.3389/fphar.2021.666348 (date from earlier preprint)
Animal dosing study with an obese dog model concluding that ivermectin maintenance doses should be based on lean body weight and not the total body weight in obese subjects, while the loading dose should be based on the total body weight.
Bousquet-Mélou et al., 11 Jan 2021, peer-reviewed, 5 authors.
Abstract: Title: Large Impact of obesity on the disposition of ivermectin, moxidectin
and eprinomectin in a canine model: relevance for COVID-19 patients.
Short running title: obesity and pharmacokinetics of ivermectin, moxidectin and
A. Bousquet-Mélou1, A Lespine1, J-F Sutra1, I Bargues1, P-L. Toutain1,3
INTHERES, Université de Toulouse, INRAE, ENVT, Toulouse, France.
The Royal Veterinary College, Hawkshead Campus, Hatfield, Herts., AL9 7TA,
P-L Toutain: http://orcid.org/0000-0002-8846-8892
*Corresponding author: Pierre-Louis Toutain*
E-mail to : firstname.lastname@example.org Fax: +33 561 19 39 17
Word count: 3880
Bullet point summary:
‘What is already known’,
The parasicicide Ivermectin is currently being evaluated for the prevention
and treatment of COVID-19, a condition for which obesity is a major risk
Dosages of ivermectin and moxidectin, an analog of ivermectin, are based on
total body weight and there are no recommendations to adjust dosage in
‘What this study adds’
Using a canine model of obesity, it was shown that the absolute value
(expressed in L/day) of plasma clearance is unchanged for moxidectin and
reduced for ivermectin in obesity compared to control conditions, whilst
steady-state volumes of distribution (expressed in L) were increased.
It is suggested that maintenance doses of ivermectin and moxidectin that are
controlled by clearance must be based on lean body weight (individual flat
dose) while the loading doses that are controlled by the volume of distribution
should be based on actual total body weight.
Background and Purpose:
Based on in vitro data, ivermectin (IVM) has been proposed for the prevention and
treatment of COVID-19, a condition for which obesity is a major risk factor. 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 and two analog compounds, moxidectin (MOX) and eprinomectin
An experimental model of obesity in dogs was based on a high calorie diet. IVM,
MOX and EPR were administered intravenously, simultaneously 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 and reduced for IVM and EPR, compared to the initial control state. When
body weight (L/day/kg), plasma clearance was reduced by 42, 55 and
63%, for MOX, IVM and EPR, respectively. In contrast, the steady-state volume of
distribution was markedly increased in absolute values (L) by obesity.
Conclusion and Implications:
For IVM and MOX, the obese dog model suggests that the maintenance dose should
not be adjusted by total body weight in the obese subject but should be based on
lean body weight. On the other hand, the loading dose should be computed based
on the total body weight of the obese subject.
Cld: Clearance of distribution
IVM : Ivermectin
LBW: Lean Body Weight
MRT: Mean Residence Time
Total Body Weight: TBW
Vc: Volume of the central compartment
V2 & V3: Volume of..
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