title: Pharmacokinetic studies with a dual-release formulation of levodopa, a novel principle in the treatment of Parkinson's disease.
abstract: The objectives of the two studies reported here were the investigation of the influence of tablet breaking and food on the pharmacokinetics of levodopa and 3-O-methyldopa (3-OMD) after administration of a new levodopa/benserazide formulation with a biphasic drug delivery profile (Madopar DR). Both studies had an open-label, randomised, two-way crossover design and were conducted in 12 healthy young subjects. The pharmacokinetics of levodopa and 3-OMD after one intact or two halved tablets were very similar with average Cmax and tmax 1.9 mg x l(-1) and 1.2 h, respectively. Administration of the formulation after a standard breakfast did not influence the extent of levodopa absorption but increased the absorption rate. Cmax and tmax were on average 2.1 mg x l(-1) and 1.3 h, respectively, in the fed condition and 1.5 mg x l(-1) and 2.5 h in the fasted condition. The presence of food did not markedly affect the plateau in levodopa levels between about 1 and 3 h after intake. In conclusion, the release characteristics in healthy subjects of the new levodopa/benserazide formulation are influenced only to a minor extent by concomitant intake of food or by tablet breaking.
authors.affiliation: Clin-Pharma Research Ltd., Birsfelden, Switzerland. cprch@datacomm.ch
authors.forename: J
authors.initials: J
authors.lastname: Dingemanse
authors.forename: C H
authors.initials: CH
authors.lastname: Kleinbloesem
authors.forename: C
authors.initials: C
authors.lastname: Crevoisier
authors.forename: G
authors.initials: G
authors.lastname: Lankhaar
authors.forename: U E
authors.initials: UE
authors.lastname: Gasser
mesh_terms: D000293:Adolescent; D000328:Adult; D000978:Antiparkinson Agents / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D018592:Cross-Over Studies; D003692:Delayed-Action Preparations; D005260:Female; D005502:Food; D006801:Humans; D007980:Levodopa / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D008297:Male; D010300:Parkinson Disease / Q000188:drug therapy* / Q000378:metabolism; D013607:Tablets; D014443:Tyrosine / Q000031:analogs & derivatives* / Q000493:pharmacokinetics
chemical_list: D000978:Antiparkinson Agents; D003692:Delayed-Action Preparations; D013607:Tablets; D014443:Tyrosine; D007980:Levodopa; C008404:3-methoxytyrosine