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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., Frontiers in Pharmacology, doi:10.3389/fphar.2021.666348 (date from preprint)
Jan 2021  
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Ivermectin for COVID-19
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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. Contact:
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A Large Impact of Obesity on the Disposition of Ivermectin, Moxidectin and Eprinomectin in a Canine Model: Relevance for COVID-19 Patients
Alain Bousquet-Mélou, Anne Lespine, Jean-François Sutra, Isabelle Bargues, Pierre-Louis Toutain
Frontiers in Pharmacology, doi:10.3389/fphar.2021.666348
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.
ETHICS STATEMENT The animal study was reviewed and approved. No specific animal experiments were carried out. The publication is based on a more advanced and focused analysis of data published in 2009 in the form of a Meeting Abstract and which was incorporated in a pharmacy thesis defended in 2011. All animal procedures were conducted in accordance with accepted standards of humane animal care required at that time under agreement number 31-242 for animal experimentation from the French Ministry of Agriculture. AUTHOR CONTRIBUTIONS AB-M was responsible for the study design and contributed to data analysis and interpretation. AL and J-FS were responsible for analytical quantification of the investigated substances. IB conducted the animal phase and managed the data sets. P-LT contributed to data analysis and interpretation and he wrote the first draft of the manuscript. All co-authors made intellectual input into the study and critically reviewed several drafts of the manuscript. SUPPLEMENTARY MATERIAL The Supplementary Material for this article can be found online at: full#supplementary-material Conflict of Interest: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. Copyright © 2021 Bousquet-Mélou, Lespine, Sutra, Bargues and Toutain. This is an open-access article distributed under..
Alvinerie, Sutra, Badri, Galtier, Determination of Moxidectin in Plasma by High-Performance Liquid Chromatography with Automated Solidphase Extraction and Fluorescence Detection, J. Chromatogr. B: Biomed. Sci. Appl, doi:10.1016/0378-4347(95)00294-5
Bargues, Influence De L'obesite Sur Les Parametres Pharmacocinetiques De Trois Substances Antiparasitaires Lipophiles
Bargues, Lespine, Toutain, Bousquet-Melou, Influence of Obesity on the Pharmacokinetics of Anthelmintic Macrocyclic Lactones in Dogs, J. Vet. Pharmacol. Ther
Baudou, Lespine, Durrieu, André, Gandia et al., Serious Ivermectin Toxicity and Human ABCB1 Nonsense Mutations, N. Engl. J. Med, doi:10.1056/NEJMc1917344
Bernigaud, Fang, Fischer, Lespine, Aho et al., Preclinical Study of Single-Dose Moxidectin, a New Oral Treatment for Scabies: Efficacy, Safety, and Pharmacokinetics Compared to Two-Dose Ivermectin in a Porcine Model, Plos Negl. Trop. Dis, doi:10.1371/journal.pntd.0005030
Bray, Rayner, Noël, Jans, Wagstaff, Ivermectin and COVID-19: A Report in Antiviral Research, Widespread Interest, an FDA Warning, Two Letters to the Editor and the Authors' Responses, Antiviral Res, doi:10.1016/j.antiviral.2020.104805
Caly, Druce, Catton, Jans, Wagstaff, The FDA-Approved Drug Ivermectin Inhibits the Replication of SARS-CoV-2 In Vitro, Antiviral Res, doi:10.1016/j.antiviral.2020.104787
Camprubí, Almuedo-Riera, Martí-Soler, Soriano, Hurtado et al., Lack of Efficacy of Standard Doses of Ivermectin in Severe COVID-19 Patients, PLoS One, doi:10.1371/journal.pone.0242184
Chaccour, Hammann, Ramón-García, Rabinovich, Ivermectin and COVID-19: Keeping Rigor in Times of Urgency, Am. J. Trop. Med. Hyg, doi:10.4269/ajtmh.20-0271
Chandler, Serious Neurological Adverse Events after Ivermectin-Do They Occur beyond the Indication of Onchocerciasis?, Am. J. Trop. Med. Hyg, doi:10.4269/ajtmh.17-0042
Chawla, Rizzo, Zalocusky, Keebler, Chia et al., Descriptive Epidemiology of 16,780 Hospitalized COVID-19 Patients in the United States, doi:10.1101/2020.07.17.20156265
Cheymol, Effects of Obesity on Pharmacokinetics Implications for Drug Therapy, Clin. Pharmacokinet, doi:10.2165/00003088-200039030-00004
Cupp, Sauerbrey, Richards, Elimination of Human Onchocerciasis: History of Progress and Current Feasibility Using Ivermectin (Mectizan ® ) Monotherapy, Acta Tropica, doi:10.1016/j.actatropica.2010.08.009
Di Filippo, De Lorenzo, D'amico, Sofia, Roveri et al., COVID-19 Is Associated with Clinically Significant Weight Loss and Risk of Malnutrition, Independent of Hospitalisation: A post-hoc Analysis of a Prospective Cohort Study, Clin. Nutr, doi:10.1016/j.clnu.2020.10.043
Dubois, Bertrand, Mentré, Mathematical Expressions of the Pharmacokinetic and Pharmacodynamic Models Implemented in the PFIM Software
Duthaler, Suenderhauf, Karlsson, Hussner, Meyer Zu Schwabedissen et al., Population Pharmacokinetics of Oral Ivermectin in Venous Plasma and Dried Blood Spots in Healthy Volunteers, Br. J. Clin. Pharmacol, doi:10.1111/bcp.13840
Elmogy, Fayed, Marzok, Rashad, Oral Ivermectin in the Treatment of Scabies, Int. J. Dermatol, doi:10.1046/j.1365-4362.1999.00865.x
Fawcett, Ivermectin Use in Scabies, Am. Fam. Physician
Fox, Ivermectin: Uses and Impact 20 Years on, Curr. Opin. Infect. Dis, doi:10.1097/QCO.0b013e328010774c
Green, Duffull, What Is the Best Size Descriptor to Use for Pharmacokinetic Studies in the Obese?, Br. J. Clin. Pharmacol, doi:10.1111/j.1365-2125.2004.02157.x
Guzzo, Furtek, Porras, Chen, Tipping et al., Safety, Tolerability, and Pharmacokinetics of Escalating High Doses of Ivermectin in Healthy Adult Subjects, J. Clin. Pharmacol, doi:10.1177/009127002401382731
Gwee, Duffull, Zhu, Tong, Cranswick et al., Population Pharmacokinetics of Ivermectin for the Treatment of Scabies in Indigenous Australian Children, Plos Negl. Trop. Dis, doi:10.1371/journal.pntd.0008886
Han, Duffull, Kirkpatrick, Green, Dosing in Obesity: A Simple Solution to a Big Problem, Clin. Pharmacol. Ther, doi:10.1038/sj.clpt.6100381
Hanley, Abernethy, Greenblatt, Effect of Obesity on the Pharmacokinetics of Drugs in Humans, Clin. Pharmacokinet, doi:10.2165/11318100-000000000-00000
He, Qian, Wong, Bai, He et al., N-in-1 Dosing Pharmacokinetics in Drug Discovery: Experience, Theoretical and Practical Considerations, J. Pharm. Sci, doi:10.1002/jps.21196
Heidary, Gharebaghi, Ivermectin: a Systematic Review from Antiviral Effects to COVID-19 Complementary Regimen, J. Antibiot, doi:10.1038/s41429-020-0336-z
Hill, Abdulamir, Ahmed, Asghar, Babalola et al., Meta-analysis of Randomized Trials of Ivermectin to Treat SARS-CoV-2 Infection, doi:10.21203/
Hoffmann, Mösbauer, Hofmann-Winkler, Kaul, Kleine-Weber et al., Chloroquine Does Not Inhibit Infection of Human Lung Cells with SARS-CoV-2, Nature, doi:10.1038/s41586-020-2575-3
Hutmacher, Kowalski, Covariate Selection in Pharmacometric Analyses: a Review of Methods: Covariate Selection in Pharmacometric Analysis, Br. J. Clin. Pharmacol, doi:10.1111/bcp.12451
Ivermectin, A Roadmap for the Development of Ivermectin as a Complementary Malaria Vector Control Tool, Am. J. Trop. Med. Hyg, doi:10.4269/ajtmh.19-0620
Jan, Cheng, Juang, Ma, Wu et al., Identification of Existing Pharmaceuticals and Herbal Medicines as Inhibitors of SARS-CoV-2 Infection, Proc. Natl. Acad. Sci, doi:10.1073/pnas.2021579118
Kern, Schöning, Chaccour, Hammann, Modeling of SARS-CoV-2 Treatment Effects for Informed Drug Repurposing, Front. Pharmacol, doi:10.3389/fphar.2021.625678
Khaodhiar, Mccowen, Blackburn, Obesity and its Comorbid Conditions, Clin. Cornerstone, doi:10.1016/s1098-3597(99)90002-9
Knibbe, Brill, Van Rongen, Diepstraten, Van Der Graaf et al., Drug Disposition in Obesity: Toward Evidence-Based Dosing, Annu. Rev. Pharmacol. Toxicol, doi:10.1146/annurev-pharmtox-010814-124354
Król, Speakman, Isotope Dilution Spaces of Mice Injected Simultaneously with Deuterium, Tritium and Oxygen-18, J. Exp. Biol, doi:10.1242/jeb.202.20.2839
Lallemand, Lespine, Alvinerie, Bousquet-Melou, Toutain, Estimation of Absolute Oral Bioavailability of Moxidectin in Dogs Using a Semi-simultaneous Method: Influence of Lipid Co-administration
Lo, Fink, Williams, Blodinger, Pharmacokinetic Studies of Ivermectin: Effects of Formulation, Vet. Res. Commun, doi:10.1007/BF02215150
López-Medina, López, Hurtado, Dávalos, Ramirez et al., Effect of Ivermectin on Time to Resolution of Symptoms Among Adults with Mild COVID-19: A Randomized Clinical Trial, JAMA, doi:10.1001/jama.2021.3071
Mahmood, Prediction of Clearance and Volume of Distribution in the Obese from normal Weight Subjects: an Allometric Approach, Clin. Pharmacokinet, doi:10.2165/11631630-000000000-0000010.1007/bf03261929
Mawby, Bartges, D'avignon, Laflamme, Moyers et al., Comparison of Various Methods for Estimating Body Fat in Dogs, J. Am. Anim. Hosp. Assoc, doi:10.5326/0400109
Meeuwsen, Horgan, The Relationship between BMI and Percent Body Fat, Measured by Bioelectrical Impedance, in a Large Adult Sample Is Curvilinear and Influenced by Age and Sex, Clin. Nutr, doi:10.1016/j.clnu.2009.12.011
Mellon, Hermet, Toutain, Dulioust, Lespine, Scabies in an Obese Patient: How Should the Ivermectin Dosing Be Adapted?, Med. Mal Infect, doi:10.1016/j.medmal.2018.09.007
Miller, Bauer, Hartz, Modulation of P-Glycoprotein at the Blood-Brain Barrier: Opportunities to Improve Central Nervous System Pharmacotherapy, Pharmacol. Rev, doi:10.1124/pr.107.07109
Milton, Hamley, Walker, Basáñez, Moxidectin: an Oral Treatment for Human Onchocerciasis, Expert Rev. Anti-infective Ther, doi:10.1080/14787210.2020.1792772
Momekov, Momekova, Ivermectin as a Potential COVID-19 Treatment from the Pharmacokinetic point of View: Antiviral Levels Are Not Likely Attainable with Known Dosing Regimens, Biotechnol. Biotechnological Equipment, doi:10.1080/13102818.2020.1775118
Muñoz, Ballester, Antonijoan, Gich, Rodríguez et al., Safety and Pharmacokinetic Profile of Fixed-Dose Ivermectin with an Innovative 18mg Tablet in Healthy Adult Volunteers, Plos Negl. Trop. Dis, doi:10.1371/journal.pntd.0006020
Ménez, Sutra, Prichard, Lespine, Relative Neurotoxicity of Ivermectin and Moxidectin in Mdr1ab (−/−) Mice and Effects on Mammalian GABA(A) Channel Activity, Plos Negl. Trop. Dis, doi:10.1371/journal.pntd.0001883
Navarro, Camprubí, Requena-Méndez, Buonfrate, Giorli et al., Safety of High-Dose Ivermectin: a Systematic Review and Meta-Analysis, J. Antimicrob. Chemother, doi:10.1093/jac/dkz524
Osto, Lutz, Translational Value of Animal Models of Obesity-Focus on Dogs and Cats, Eur. J. Pharmacol, doi:10.1016/j.ejphar.2015.03.036
Popkin, Corvalan, Grummer-Strawn, Dynamics of the Double burden of Malnutrition and the Changing Nutrition Reality, Lancet, doi:10.1016/S0140-6736(19)32497-3
Popkin, Du, Green, Beck, Algaith et al., Individuals with Obesity and COVID-19: A Global Perspective on the Epidemiology and Biological Relationships, Obes. Rev. obr, doi:10.1111/obr.13128
Prichard, Ménez, Lespine, Moxidectin and the Avermectins: Consanguinity but Not Identity, Int. J. Parasitol. Drugs Drug Resist, doi:10.1016/j.ijpddr.2012.04.001
Rhea, Salameh, Logsdon, Hanson, Erickson et al., Blood-Brain Barriers in Obesity, AAPS J, doi:10.1208/s12248-017-0079-3
Rocchini, Moorehead, Wentz, Deremer, Obesityinduced Hypertension in the Dog, Hypertension, doi:10.1161/01.hyp.9.6_pt_2.iii64
Savic, Karlsson, Importance of Shrinkage in Empirical Bayes Estimates for Diagnostics: Problems and Solutions, AAPS J, doi:10.1208/s12248-009-9133-0
Schinkel, Smit, Van Tellingen, Beijnen, Wagenaar et al., Disruption of the Mouse Mdr1a P-Glycoprotein Gene Leads to a Deficiency in the Blood-Brain Barrier and to Increased Sensitivity to Drugs, Cell, doi:10.1016/0092-8674(94)90212-7
Schulz, Coulibaly, Schindler, Wimmersberger, Keiser, Pharmacokinetics of Ascending Doses of Ivermectin in Trichuris Trichiura-Infected Children Aged 2-12 Years, J. Antimicrob. Chemother, doi:10.1093/jac/dkz083
Solomon, FDA Letter to Stakeholders: Do Not Use Ivermectin Intended for Animals as Treatment for COVID-19 in Humans
Sutra, Chartier, Galtier, Alvinerie, Determination of Eprinomectin in Plasma by High-Performance Liquid Chromatography with Automated Solid Phase Extraction and Fluorescence Detection, Analyst, doi:10.1039/a802093k
Toutain, Bousquet-Melou, Volumes of Distribution, J. Vet. Pharmacol. Ther, doi:10.1111/j.1365-2885.2004.00602.x
Verwaerde, Sénard, Galinier, Rougé, Massabuau et al., Changes in Short-Term Variability of Blood Pressure and Heart Rate during the Development of Obesity-Associated Hypertension in High-Fat Fed Dogs, J. Hypertens, doi:10.1097/00004872-199917080-00013
Vora, Arora, Behera, Tripathy, White Paper on Ivermectin as a Potential Therapy for COVID-19, Indian J. Tuberculosis, doi:10.1016/j.ijtb.2020.07.031
Wadman, Why COVID-19 Is More Deadly in People with Obesity-Even if They're Young, Science, doi:10.1126/science.abe7010
Wadman, Why Obesity Worsens COVID-19, Science, doi:10.1126/science.369.6509.1280
Williamson, Walker, Bhaskaran, Bacon, Bates et al., Factors Associated with COVID-19-Related Death Using OpenSAFELY, Nature, doi:10.1038/s41586-020-2521-4
Xia, Xiao, Liu, Pimprale, Fox et al., Comparison of Species Differences of P-Glycoproteins in Beagle Dog, Rhesus Monkey, and Human Using ATPase Activity Assays, Mol. Pharmaceutics, doi:10.1021/mp050034j
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