Abstract: See discussions, stats, and author profiles for this publication at: https://www.researchgate.net/publication/11094854 Safety, Tolerability, and Pharmacokinetics of Escalating High Doses of Ivermectin in Healthy Adult Subjects Article in The Journal of Clinical Pharmacology · November 2002 DOI: 10.1177/009127002401382731 · Source: PubMed CITATIONS READS 259 6,621 9 authors, including: David Sciberras 46 PUBLICATIONS 1,387 CITATIONS Kenneth C Lasseter Clinical pharmacology of Miami 229 PUBLICATIONS 8,488 CITATIONS SEE PROFILE SEE PROFILE Some of the authors of this publication are also working on these related projects: Benazepril (Cibacen®) in man View project pharmacology View project All content following this page was uploaded by Kenneth C Lasseter on 02 December 2020. The user has requested enhancement of the The Journal of Clinical Pharmacology http://jcp.sagepub.com/ Safety, tolerability, and pharmacokinetics of escalating high doses of ivermectin in healthy adult subjects CA Guzzo, CI Furtek, AG Porras, C Chen, R Tipping, CM Clineschmidt, DG Sciberras, JY Hsieh and KC Lasseter J Clin Pharmacol 2002 42: 1122 The online version of this article can be found at: http://jcp.sagepub.com/content/42/10/1122 Published by: http://www.sagepublications.com On behalf of: American College of Clinical Pharmacology Additional services and information for The Journal of Clinical Pharmacology can be found at: Email Alerts: http://jcp.sagepub.com/cgi/alerts Subscriptions: http://jcp.sagepub.com/subscriptions Reprints: http://www.sagepub.com/journalsReprints.nav Permissions: http://www.sagepub.com/journalsPermissions.nav GUZZO HIGH PHARMACOKINETICS DOSES ET ALOF IVERMECTIN AND PHARMACODYNAMICS IN ADULTS Safety, Tolerability, and Pharmacokinetics of Escalating High Doses of Ivermectin in Healthy Adult Subjects Cynthia A. Guzzo, MD, Christine I. Furtek, BS, Arturo G. Porras, PhD, Cong Chen, PhD, Robert Tipping, MS, Coleen M. Clineschmidt, BA, David G. Sciberras, PhD, John Y-K. Hsieh, PhD, and Kenneth C. Lasseter, MD Safety and pharmacokinetics (PK) of the antiparasitic drug ivermectin, administered in higher and/or more frequent doses than currently approved for human use, were evaluated in a double-blind, placebo-controlled, dose escalation study. Subjects (n = 68) were assigned to one of four panels (3:1, ivermectin/placebo): 30 or 60 mg (three times a week) or 90 or 120 mg (single dose). The 30 mg panel (range: 347-594 µg/kg) also received a single dose with food after a 1-week washout. Safety assessments addressed both known ivermectin CNS effects and general toxicity. The primary safety endpoint was mydriasis, accurately quantitated by pupillometry. Ivermectin was generally well tolerated, with no indication of associated CNS toxicity for doses up to 10 times the highest FDA-approved dose of 200 µg/kg. All dose regimens had a mydriatic effect similar to placebo. Adverse experiences were similar between ivermectin and placebo and did not increase with dose. Following single doses of 30 to 120 mg, AUC and Cmax were generally dose proportional, with tmax ~4 hours and t1/2 ~18 hours. The geometric mean AUC of 30 mg ivermectin was 2.6 times higher when administered with food. Geometric mean AUC ratios (day 7/day 1) were 1.24 and 1.40 for the 30 and 60 mg doses, respectively, indicating that the accumulation of ivermectin given every fourth..