title: Uptake of pramipexole by human organic cation transporters.
abstract: Pramipexole is a hydrophilic, weakly basic drug, but exhibits high oral bioavailability in humans (>90%). In rats, rOct1 and rOct2 contribute toward pramipexole excretion into urine. The objective of this study was to assess whether pramipexole is a substrate for human OCT1-3. In vitro uptake studies were performed using hOCT1-MDCK monolayers, hOCT2-HEK cells and hOCT3-HEK cells. hOCT2 transported pramipexole in a high affinity manner (K(t) = 15.4 +/- 4.1 microM, J(max) = 0.476 +/- 0.028 pmol/s/cm(2)). hOCT3 transported pramipexole in a low affinity manner (K(t) = 138 +/- 31 microM, J(max) = 1.10 +/- 0.08 pmol/s/cm(2)). Although previously reported to be translocated by rOct1, pramipexole was not a substrate for hOCT1. The human intestinal absorption of pramipexole may involve transport by OCT3 and possibly OCT2. OCT2- and OCT3-mediated transport of pramipexole have implications in the drug's elimination from the kidney and distribution in the brain, respectively.
authors.affiliation: Department of Pharmaceutical Sciences, School of Pharmacy, University of Maryland, Baltimore, Maryland 21201, USA.
authors.forename: Lei
authors.initials: L
authors.lastname: Diao
authors.forename: Yan
authors.initials: Y
authors.lastname: Shu
authors.forename: James E
authors.initials: JE
authors.lastname: Polli
mesh_terms: D000818:Animals; D052160:Benzothiazoles / Q000378:metabolism* / Q000493:pharmacokinetics* / Q000494:pharmacology; D001692:Biological Transport / Q000187:drug effects; D002460:Cell Line; D003345:Corticosterone / Q000494:pharmacology; D004285:Dogs; D018491:Dopamine Agonists / Q000493:pharmacokinetics / Q000494:pharmacology; D006801:Humans; D027701:Organic Cation Transport Proteins / Q000378:metabolism*; D027702:Organic Cation Transporter 1 / Q000378:metabolism; D000075102:Organic Cation Transporter 2; D000077487:Pramipexole
chemical_list: D052160:Benzothiazoles; D018491:Dopamine Agonists; D027701:Organic Cation Transport Proteins; D027702:Organic Cation Transporter 1; D000075102:Organic Cation Transporter 2; C491013:SLC22A2 protein, human; D000077487:Pramipexole; D003345:Corticosterone