title: The effect of peripheral enzyme inhibitors on levodopa concentrations in blood and CSF.
abstract: Levodopa combined with a dopa-decarboxylase inhibitor, such as carbidopa, shifts the metabolism to the COMT pathway. Adding the peripheral acting COMT inhibitor entacapone provides improvement for patients with PD suffering from motor fluctuations. We studied the effects of the enzyme inhibitors entacapone and carbidopa on the levodopa concentrations in CSF and in blood. Five PD patients with wearing-off underwent lumbar drainage and intravenous microdialysis. Samples were taken 12 h daily for 3 days. Day 1; intravenous levodopa was given, day 2; additional oral entacapone 200 mg tid, day 3; additional oral entacapone 200 mg tid and carbidopa 25 mg bid. Levodopa in CSF and in dialysates was analysed. The AUC for levodopa increased both in blood and CSF when additional entacapone was given alone and in combination with carbidopa. The C(max) of levodopa in both CSF and blood increased significantly. Additional entacapone to levodopa therapy gives an increase of C(max) in CSF and in blood. The increase is more evident when entacapone is combined with carbidopa.
authors.affiliation: Department of Neurology, University Hospital, Linköping, Sweden.
authors.forename: Maria
authors.initials: M
authors.lastname: Nord
authors.forename: Peter
authors.initials: P
authors.lastname: Zsigmond
authors.forename: Anita
authors.initials: A
authors.lastname: Kullman
authors.forename: Kerstin
authors.initials: K
authors.lastname: Arstrand
authors.forename: Nil
authors.initials: N
authors.lastname: Dizdar
mesh_terms: D000284:Administration, Oral; D000368:Aged; D000369:Aged, 80 and over; D000978:Antiparkinson Agents / Q000097:blood / Q000134:cerebrospinal fluid / Q000627:therapeutic use; D019540:Area Under Curve; D002396:Catechols / Q000008:administration & dosage; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000008:administration & dosage*; D005260:Female; D006801:Humans; D007980:Levodopa / Q000097:blood / Q000134:cerebrospinal fluid / Q000627:therapeutic use; D008297:Male; D008619:Mepivacaine / Q000008:administration & dosage; D017551:Microdialysis / Q000379:methods; D008875:Middle Aged; D009570:Nitriles / Q000008:administration & dosage; D010300:Parkinson Disease / Q000097:blood / Q000134:cerebrospinal fluid / Q000188:drug therapy; D013997:Time Factors
chemical_list: D000978:Antiparkinson Agents; D002396:Catechols; D004791:Enzyme Inhibitors; D009570:Nitriles; D007980:Levodopa; C071192:entacapone; D008619:Mepivacaine