Safety and pharmacokinetic profile of fixed-dose ivermectin with an innovative 18mg tablet in healthy adult volunteers
| العنوان: | Safety and pharmacokinetic profile of fixed-dose ivermectin with an innovative 18mg tablet in healthy adult volunteers |
|---|---|
| المؤلفون: | Muñoz, Jose, Ballester, Maria Rosa, Antonijoan Arbós, Rosa Ma., Gich, Ignasi, Rodríguez, Montse, Colli, Enrico, Gold, Silvia, Krolewiecki, Alejandro J., Universitat Autònoma de Barcelona |
| المساهمون: | Universitat de Barcelona |
| المصدر: | PLoS Neglected Tropical Diseases r-IIB SANT PAU. Repositorio Institucional de Producción Científica del Instituto de Investigación Biomédica Sant Pau instname Dipòsit Digital de Documents de la UAB Universitat Autònoma de Barcelona Recercat. Dipósit de la Recerca de Catalunya Dipòsit Digital de la UB Universidad de Barcelona CONICET Digital (CONICET) Consejo Nacional de Investigaciones Científicas y Técnicas instacron:CONICET PLoS Neglected Tropical Diseases, Vol 12, Iss 1, p e0006020 (2018) |
| بيانات النشر: | Public Library of Science (PLoS), 2018. |
| سنة النشر: | 2018 |
| مصطلحات موضوعية: | Male, 0301 basic medicine, Time Factors, Physiology, Phases of clinical research, Pharmacology, Pharmacokinetic Analysis, Body Mass Index, Plasma, 0302 clinical medicine, Ivermectin, Elimination Half-Life Calculation, Medicine and Health Sciences, Administration of drugs, Chromatography, High Pressure Liquid, Lymphatic filariasis, Anthelmintics, Pharmaceutics, lcsh:Public aspects of medicine, purl.org/becyt/ford/3.1 [https], Healthy Volunteers, Body Fluids, Medicina Básica, Blood, Infectious Diseases, Physiological Parameters, Research Design, purl.org/becyt/ford/3 [https], Female, Administració de medicaments, Anatomy, Research Article, Tablets, medicine.drug, Adult, Farmacología y Farmacia, lcsh:Arctic medicine. Tropical medicine, Drug Administration, CIENCIAS MÉDICAS Y DE LA SALUD, Drug-Related Side Effects and Adverse Reactions, lcsh:RC955-962, Clinical Research Design, 030231 tropical medicine, Cmax, Research and Analysis Methods, Blood Plasma, Beverages, Young Adult, 03 medical and health sciences, Drug Therapy, Pharmacokinetics, NEGLECTED TROPICAL DISEASES, medicine, Humans, Adverse effect, Nutrition, Tea, Farmacocinètica, business.industry, Body Weight, Public Health, Environmental and Occupational Health, Biology and Life Sciences, lcsh:RA1-1270, medicine.disease, Diet, Bioavailability, Pharmacologic Analysis, 030104 developmental biology, Adverse Events, IVERMECTIN, HPLC, business, Onchocerciasis |
| الوصف: | Ivermectin is a pivotal drug for the control of onchocerciasis and lymphatic filariasis, which is increasingly identified as a useful drug for the control of other Neglected Tropical Diseases. Its role in the treatment of soil transmitted helminthiasis through improved efficacy against Trichuris trichiura in combination with other anthelmintics might accelerate the progress towards breaking transmission. Ivermectin is a derivative of Avermectin B1, and consists of an 80:20 mixture of the equipotent homologous 22,23 dehydro B1a and B1b. Pharmacokinetic characteristics and safety profile of ivermectin allow to explore innovative uses to further expand its utilization through mass drug administration campaigns to improve coverage rates. We conducted a phase I clinical trial with 54 healthy adult volunteers who sequentially received 2 experimental treatments using a new 18 mg ivermectin tablet in a fixed-dose strategy of 18 and 36 mg single dose regimens, compared to the standard, weight based 150–200 μg/kg, regimen. Volunteers were recruited in 3 groups based on body weight. Plasma concentrations of ivermectin were measured through HPLC up to 168 hours post treatment. Safety data showed no significant differences between groups and no serious adverse events: headache was the most frequent adverse event in all treatment groups, none of them severe. Pharmacokinetic parameters showed a half-life between 81 and 91 h in the different treatment groups. When comparing the systemic bioavailability (AUC0t and Cmax) of the reference product (WA-ref) with the other two study groups using fixed doses, we observed an overall increase in AUC0t and Cmax for the two experimental treatments of 18 mg and 36 mg. Body mass index (BMI) and weight were associated with t1/2 and V/F, probably reflecting the high liposolubility of IVM with longer retention times proportional to the presence of more adipose tissue. Systemic exposure to ivermectin (AUC0t or Cmax) was not associated with BMI or weight in our study. These findings contribute to further understand the pharmacokinetic characteristics of ivermectin, highlighting its safety across different dosing regimens. They also correlate with known pharmacokinetic parameters showing stable levels of AUC and Cmax across a wide range of body weights, which justifies the strategy of fix dosing from a pharmacokinetic perspective. Trial registration ClinicalTrials.gov NCT03173742. Author summary Current efforts for the control of poverty-related diseases provide drug treatments through mass drug administration (MDA) as a key component. Ivermectin is an antiparasitary drug which has been used to fight some of these diseases, and millions of treatments have been distributed with a favorable toxicity profile. The dosing strategy of ivermectin is based on weight, which in view of the safety characteristics of ivermectin might not be necessary, while a fix dosing strategy might improve logistics and access to the drug to those who need it. This study was conducted in healthy adult volunteers in which we compared 3 treatment regimens: the weight-based reference standard versus 2 experimental regimens of fix-dose 18 and 36 mg using 18 mg tablets. All 54 volunteers received the 3 treatments sequentially. The results confirmed that the fixed-dose regimen (both 18 mg and 36 mg) are as safe as the standard dosage and could justify the use of fix dosing regimens rather than the current weight based strategy. |
| وصف الملف: | application/pdf |
| تدمد: | 1935-2735 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::8892dc5e0de8d2dafe2d848ab2e08fe8Test https://doi.org/10.1371/journal.pntd.0006020Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....8892dc5e0de8d2dafe2d848ab2e08fe8 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 19352735 |
|---|