title: Study of the safety of methylphenidate: Focus on nephrotoxicity aspects.
abstract: OBJECTIVE
  Methylphenidate (MPD) is increasingly prescribed for the treatment of Attention Deficit Hyperactivity Disorder and there are concerns about its appropriate use. Furthermore, little is known about the potential nephrotoxicity in patients using MPD. This study aimed to investigate the safety of MPD, with focus on the possible effects of this drug on renal function.
  
  
  METHODS
  We investigated the effects of MPD on renal perfusion system and renal tubular cells through in vivo and in vitro experimental models.
  
  
  RESULTS
  In the in vivo experiments, 24 h and 48 h after MPD administration, urea, creatinine, creatinine clearance, and the fractional excretion of sodium and potassium were not changed. In the isolated kidney perfusion, MPD significantly reduced urinary flow, glomerular filtration rate and the percentage of tubular sodium transport. However, the perfusion pressure, renal vascular resistance and the percentage of tubular potassium transport were unchanged in this system. In the canine renal epithelial cell line MDCK culture, MPD was not cytotoxic and, in histopathological analysis, MPD did not promote alterations.
  
  
  CONCLUSIONS
  Our findings suggest a possible nephrotoxic effect of MPD, since it altered renal function by reducing the glomerular activity, urinary flow and sodium transport. These effects need to be further investigated in order to minimize potential harms associated with the use of MPD.
authors.affiliation: Postgraduation Program in Development and Technological Innovation in Medicines (PPGDITM), Federal University of Ceará (UFC), Brazil.
authors.forename: Luiza Herbene Macedo Soares
authors.initials: LH
authors.lastname: Salviano
authors.affiliation: Postgraduation Program in Pharmacology/UFC, Brazil.
authors.forename: Maria Isabel
authors.initials: MI
authors.lastname: Linhares
authors.affiliation: Pharmacy Course/UFC, Brazil.
authors.forename: Klistenes Alves
authors.initials: KA
authors.lastname: de Lima
authors.affiliation: Pharmacy Course/UFC, Brazil.
authors.forename: Alana Gomes
authors.initials: AG
authors.lastname: de Souza
authors.affiliation: Postgraduation Program in Pharmaceutical Sciences/UFC, Brazil.
authors.forename: Dânya Bandeira
authors.initials: DB
authors.lastname: Lima
authors.affiliation: Department of Physiology and Pharmacology/UFC, Brazil.
authors.forename: Antônio Rafael Coelho
authors.initials: AR
authors.lastname: Jorge
authors.affiliation: Postgraduation Program in Pharmaceutical Sciences/UFC, Brazil.
authors.forename: Marcus Felipe Bezerra
authors.initials: MF
authors.lastname: da Costa
authors.affiliation: Department of Physiology and Pharmacology/UFC, Brazil.
authors.forename: Adriano José Maia Chaves
authors.initials: AJ
authors.lastname: Filho
authors.affiliation: Postgraduation Program in Development and Technological Innovation in Medicines (PPGDITM), Federal University of Ceará (UFC), Brazil; Postgraduation Program in Pharmacology/UFC, Brazil; Postgraduation Program in Pharmaceutical Sciences/UFC, Brazil; Pharmacy Course/UFC, Brazil.
authors.forename: Alice Maria Costa
authors.initials: AM
authors.lastname: Martins
authors.affiliation: Postgraduation Program in Pharmacology/UFC, Brazil; Department of Physiology and Pharmacology/UFC, Brazil.
authors.forename: Helena Serra Azul
authors.initials: HS
authors.lastname: Monteiro
authors.affiliation: Postgraduation Program in Development and Technological Innovation in Medicines (PPGDITM), Federal University of Ceará (UFC), Brazil; Pharmacy Course/UFC, Brazil.
authors.forename: Teresa Maria
authors.initials: TM
authors.lastname: de Jesus Ponte Carvalho
authors.affiliation: Postgraduation Program in Development and Technological Innovation in Medicines (PPGDITM), Federal University of Ceará (UFC), Brazil; Postgraduation Program in Pharmacology/UFC, Brazil; Postgraduation Program in Pharmaceutical Sciences/UFC, Brazil; Pharmacy Course/UFC, Brazil. Electronic address: martafonteles@yahoo.com.br.
authors.forename: Marta Maria
authors.initials: MM
authors.lastname: de França Fonteles
mesh_terms: D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D000697:Central Nervous System Stimulants / Q000633:toxicity*; D003404:Creatinine / Q000378:metabolism; D004285:Dogs; D005919:Glomerular Filtration Rate / Q000187:drug effects; D006801:Humans; D066298:In Vitro Techniques; D007674:Kidney Diseases / Q000139:chemically induced* / Q000473:pathology; D007677:Kidney Function Tests; D007684:Kidney Tubules / Q000187:drug effects / Q000473:pathology; D061985:Madin Darby Canine Kidney Cells; D008297:Male; D008774:Methylphenidate / Q000633:toxicity*; D011188:Potassium / Q000378:metabolism; D051381:Rats; D012079:Renal Circulation / Q000187:drug effects; D012964:Sodium / Q000378:metabolism; D014508:Urea / Q000378:metabolism; D014563:Urodynamics / Q000187:drug effects
chemical_list: D000697:Central Nervous System Stimulants; D008774:Methylphenidate; D014508:Urea; D012964:Sodium; D003404:Creatinine; D011188:Potassium
keywords: Methylphenidate; Nephrotoxicity; Renal perfusion