A randomized controlled laboratory study on the long-term effects of methylphenidate on cardiovascular function and structure in rhesus monkeys.

Autor: Wilkinson JD; Department of Pediatrics, Vanderbilt University School of Medicine, Nashville, TN, 37232, USA., Callicott R; Animal Resource Center, University of Texas Southwestern Medical Center, Dallas, TX, 75390, USA., Salminen WF; Toxicology and Formulations, Pro Natural Brands, LLC, Victor, NY, 14564, USA., Sandhu SK; Department of Pediatrics, University of Miami Miller School of Medicine, Miami, FL, 33156, USA., Greenhaw J; Division of Systems Biology, National Center for Toxicological Research, US Food and Drug Administration, Jefferson, AR, 72079, USA., Paredes A; Office of Scientific Coordination, National Center for Toxicological Research, US Food and Drug Administration, Jefferson, AR, 72079, USA., Davis K; Toxicologic Pathology Associates, Jefferson, AR, 72079, USA., Jones Y; Office of Scientific Coordination, National Center for Toxicological Research, US Food and Drug Administration, Jefferson, AR, 72079, USA., Paule MG; Division of Neurotoxicology, National Center for Toxicological Research, US Food and Drug Administration, Jefferson, AR, 72079, USA., Slikker W Jr; Office of the Center Director, National Center for Toxicological Research, US Food and Drug Administration, Jefferson, AR, 72079, USA., Rusconi PG; Department of Pediatrics, University of Miami Miller School of Medicine, Miami, FL, 33156, USA., Czachor J; Department of Pediatrics, Wayne State University School of Medicine and Children's Hospital of Michigan, Detroit, MI, 48201, USA., Bodien A; Department of Pediatrics, Wayne State University School of Medicine and Children's Hospital of Michigan, Detroit, MI, 48201, USA., Westphal JA; Department of Pediatrics, Wayne State University School of Medicine and Children's Hospital of Michigan, Detroit, MI, 48201, USA., Dauphin DD; Department of Neurology, University of Miami Miller School of Medicine, Miami, FL, 33156, USA., Lipshultz SE; Department of Pediatrics, University at Buffalo Jacobs School of Medicine and Biomedical Sciences, Oishei Children's Hospital, Roswell Park Comprehensive Cancer Center, Buffalo, NY, 14203, USA. slipshultz@upa.chob.edu.
Jazyk: angličtina
Zdroj: Pediatric research [Pediatr Res] 2019 Feb; Vol. 85 (3), pp. 398-404. Date of Electronic Publication: 2018 Dec 17.
DOI: 10.1038/s41390-018-0256-9
Abstrakt: Background: Whether long-term methylphenidate (MPH) results in any changes in cardiovascular function or structure can only be properly addressed through a randomized trial using an animal model which permits elevated dosing over an extended period of time.
Methods: We studied 28 male rhesus monkeys (Macaca mulatta) approximately 7 years of age that had been randomly assigned to one of three MPH dosages: vehicle control (0 mg/kg, b.i.d., n = 9), low dose (2.5 mg/kg, b.i.d., n = 9), or high dose (12.5 mg/kg, b.i.d., n = 10). Dosage groups were compared on serum cardiovascular and inflammatory biomarkers, electrocardiograms (ECGs), echocardiograms, myocardial biopsies, and clinical pathology parameters following 5 years of uninterrupted dosing.
Results: With the exception of serum myoglobin, there were no statistical differences or apparent dose-response trends in clinical pathology, cardiac inflammatory biomarkers, ECGs, echocardiograms, or myocardial biopsies. The high-dose MPH group had a lower serum myoglobin concentration (979 ng/mL) than either the low-dose group (1882 ng/mL) or the control group (2182 ng/mL). The dose response was inversely proportional to dosage (P = .0006).
Conclusions: Although the findings cannot be directly generalized to humans, chronic MPH exposure is unlikely to be associated with increased cardiovascular risk in healthy children.
Databáze: MEDLINE
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