title: Pharmacokinetic evaluation of pramipexole.
abstract: BACKGROUND
  Immediate-release (IR) pramipexole dihydrochloride is indicated for the treatment of signs and symptoms of idiopathic Parkinson's disease (PD). It is administered alone (without levodopa) or in combination with levodopa, during the entire progress of the disease, up to an advanced stage. Currently, it is also indicated for the treatment of moderate-to-severe primary restless legs syndrome (RLS). An extended-release (ER) formulation of pramipexole has been developed to allow a once-daily administration and to provide more stable dopaminergic stimulation in PD patients.
  
  
  METHODS
  This review summarizes the overall pharmacokinetic profile of pramipexole for both the IR and ER formulations. Also discussed are the clinically relevant determinants of pramipexole peripheral pharmacokinetics and the potential role of genetic and clinical determinants in drug efficacy.
  
  
  CONCLUSIONS
  Pramipexole is a non-ergot agonist with selective affinity for dopamine receptors of the D2 subfamily, in particular D3. Pramipexole has a very low affinity for serotoninergic 5-HT2A and 5-HT2B receptors, as well as D1-type receptors. Furthermore, it does not carry the risk to induce valvular heart disease or pulmonary and retroperitoneal fibrosis, seen with long-term use of the ergot-derived dopamine agonists. The recent introduction of a once-daily formulation poses significant advantages for patients, reflected by relatively stable plasma levels. The most obvious benefit is convenience of use and better adherence to treatment schedule. Additional advantages could include the opportunity to provide more continuous drug delivery in a fashion that could help minimize dyskinesia risk, if the drug is used early in the disease course.
authors: Department for Parkinson Disease, IRCCS San Camillo, Venice, Italy. angelo3000@yahoo.com
authors: Angelo
authors: A
authors: Antonini
authors: Daniela
authors: D
authors: Calandrella
mesh_terms: D052160:Benzothiazoles / Q000493:pharmacokinetics* / Q000494:pharmacology*; D018491:Dopamine Agonists / Q000493:pharmacokinetics* / Q000494:pharmacology*; D016503:Drug Delivery Systems / Q000379:methods; D004341:Drug Evaluation; D064420:Drug-Related Side Effects and Adverse Reactions / Q000378:metabolism; D023381:Endpoint Determination; D006349:Heart Valve Diseases / Q000188:drug therapy; D006801:Humans; D007980:Levodopa / Q000627:therapeutic use; D010300:Parkinson Disease / Q000188:drug therapy; D010597:Pharmacogenetics; D000077487:Pramipexole; D011954:Receptors, Dopamine / Q000187:drug effects / Q000378:metabolism; D012148:Restless Legs Syndrome / Q000188:drug therapy
chemical_list: D052160:Benzothiazoles; D018491:Dopamine Agonists; D011954:Receptors, Dopamine; D007980:Levodopa; D000077487:Pramipexole