ABSTRACT
BACKGROUND: There are doubts wether generic medications have the same bioavailability and efficacy compared with the original drugs developed by pharmaceutical companies with research capabilities. AIM: To compare the pharmacokinetics and clinical (motor) responses of Sinemet and Grifoparkin (generic carbidopa/levodopa 250/25 mg) in patients with advanced Parkinson's disease. PATIENTS AND METHODS: Patients were randomly assigned to Sinemet (15 patients 62 +/- 12 years old; mean disease duration 11 +/- 7 years) or Grifoparkin (15 patients, 64 +/- 11 years old; mean disease duration 12 +/- 4 years) groups. Medication and food were withheld 12 h before the study. Fifteen blood samples were collected (starting 9 AM) immediately before (sample 1, t = 0 min) and after (samples 2-15, t = 20-360 min) oral administration of a single dose of Sinemet or Grifoparkin, and plasmatic L-DOPA was quantified using HPLC with electrochemical detection. Additionally, each patient was clinically evaluated every 20 minutes, using the tapping test and the unified Parkinson's disease scale Hoehn & Yarh. RESULTS: Tmax (time at which the maximal L-DOPA concentration was reached) were 69 +/- 12 min and 64 +/- 11 min for Sinemet and Grifoparkin respectively (NS). Cmax (maximal L-DOPA concentration reached) was 3161 +/- 345 ng/ml for Sinemet and 3274 +/- 520 ng/ml for Grifoparkin (NS). The t1/2 (half life time), CL (clearance) and volume of distribution (Vd) values calculated were 159 +/- 32 min, 51.7 +/- 5.1 1/h and 3.6 +/- 1.2 l/kg for Sinemet and 161 +/- 48 min, 58.7 +/- 8 l/h and 3.0 +/- 0.7 l/kg for Grifoparkin (NS). UPDRS-III value for the best on state and for the worst off state were 23 +/- 11 and 50 +/- 19 for Sinemet and 20 +/- 7 and 46 +/- 13 for Grifoparkin respectively (NS). CONCLUSION: The results obtained showed that both drugs are bioequivalent in patients with advanced Parkinson's disease.
Subject(s)
Humans , Male , Female , Middle Aged , Antiparkinson Agents/pharmacokinetics , Carbidopa/pharmacokinetics , Parkinson Disease/metabolism , Levodopa/pharmacokinetics , Antiparkinson Agents/administration & dosage , Carbidopa/administration & dosage , Drug Combinations , Biological Availability , Parkinson Disease/drug therapy , Levodopa/administration & dosage , Double-Blind MethodABSTRACT
La levodopa continúa siendo la terapia más efectiva en la enfermedad de Parkinson (EP), el desarrollo de diferentes formulaciones ha respondido a las distintas necesidades de los pacientes con EP avanzada. Las formulaciones líquidas o dispersables se han orientado a optimizar la farmacocinética periférica de la levodopa. Se diseñaron 4 experiencias diferentes: la primera con soluciones a diferentes concentraciones de levodopa (1 a 4 mg/ml); el segundo grupo soluciones a 1 mg/ml de levodopa con y sin filtrarlas; el tercero, igual concentración con las diferentes formas comerciales; y 4 las soluciones preparadas por los pacientes
Subject(s)
Humans , Carbidopa/pharmacokinetics , Levodopa/pharmacokinetics , Parkinson Disease/drug therapy , Drug Stability , Parkinson Disease/metabolism , SolubilityABSTRACT
O parkinsonismo idiopático (doença de Parkinson) e secundário, ou seja, que apresenta etiologia conhecida (pós-encefalítico, por toxinas, por drogas ou por algumas doenças degenerativas) såo processos neurodegenerativos que afetam progressivamente as funçÆes motoras normais do indivíduo. Neste trabalho, os aspéctos clínicos, etiológicos, fisiopatológicos e principalmente a descriçåo do arsenal farmacológico e as medidas utilizadas no combate ou retardo medicamentoso do parkinsonismo såo abordados e discutidos