RESUMO
BACKGROUND: Observational studies suggest that single-tablet formulations are associated with improved adherence versus the same components taken as separate tablets. The objective of this study was to compare adherence in patients with Parkinson's disease (PD) receiving levodopa therapy as levodopa/carbidopa/entacapone tablets (LCE) versus levodopa/carbidopa (LC) tablets and entacapone (E) as separate tablets (LC and E). METHODS: This was a retrospective, observational cohort study using a large health insurance claims database. Subjects included persons with a PD diagnosis who were receiving LC without E and then received either an add-on therapy with E as a separate tablet (LC and E) or LCE as one tablet (LCE). The primary study outcome was treatment adherence, estimated from pharmacy refills based on the 'percent of days covered' (PDC) with LCE or LC and E during follow-up and compared for patients receiving LCE and LC and E using multivariate regression analyses. RESULTS: In multivariate analyses controlling for differences between groups in baseline characteristics, including pre-index dosage of and adherence with LC, receipt of LCE (n = 388) was associated with 79% lower mean non-adherence during follow-up (95% CI: 73-83%; p < 0.001) versus LC and E (n = 823), 86% lower odds of unsatisfactory adherence (95% CI: 80-91%; p < 0.001), and a 26% lower risk of discontinuation (95% CI: 6-42%; p < 0.013). LIMITATIONS: This was an observational study with the inherent potential for selection bias. Pharmacy claims may not provide an accurate estimate of adherence. Requiring subjects to have a certain number of prescriptions before and after the index date may yield a sample that is not representative of all patients initiating levodopa therapy in typical clinical practice. CONCLUSIONS: Better adherence with LCE may have important implications for maintaining function in patients receiving chronic oral levodopa therapy. Further research is needed to confirm these results and examine the association between improved adherence and clinical and economic outcomes.
Assuntos
Carbidopa/administração & dosagem , Catecóis/administração & dosagem , Levodopa/administração & dosagem , Nitrilas/administração & dosagem , Doença de Parkinson/tratamento farmacológico , Cooperação do Paciente/estatística & dados numéricos , Idoso , Idoso de 80 Anos ou mais , Algoritmos , Antiparkinsonianos/administração & dosagem , Antiparkinsonianos/efeitos adversos , Carbidopa/efeitos adversos , Catecóis/efeitos adversos , Estudos de Coortes , Formas de Dosagem , Combinação de Medicamentos , Feminino , Humanos , Levodopa/efeitos adversos , Masculino , Pessoa de Meia-Idade , Nitrilas/efeitos adversos , Doença de Parkinson/epidemiologia , Estudos Retrospectivos , ComprimidosRESUMO
The authors investigated neuropsychiatric symptoms in mild cognitive impairment (MCI) from baseline data of the Investigation in the Delay to Diagnosis of AD with Exelon (InDDEx) study (n = 1,010). Neuropsychiatric symptoms were reported in 59% of subjects (Neuropsychiatric Inventory [NPI]). NPI+ subjects had significantly greater impairment on global, cognitive, and functional scores than NPI- subjects. The presence of neuropsychiatric symptoms appears to be a marker of MCI severity.
Assuntos
Doença de Alzheimer/prevenção & controle , Sintomas Comportamentais/diagnóstico , Transtornos Cognitivos/diagnóstico , Testes Neuropsicológicos/estatística & dados numéricos , Fenilcarbamatos , Idoso , Idoso de 80 Anos ou mais , Doença de Alzheimer/complicações , Doença de Alzheimer/fisiopatologia , Sintomas Comportamentais/complicações , Sintomas Comportamentais/fisiopatologia , Carbamatos/uso terapêutico , Inibidores da Colinesterase/uso terapêutico , Transtornos Cognitivos/complicações , Transtornos Cognitivos/fisiopatologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , RivastigminaRESUMO
This study sought to examine the feasibility of prolonged assessment of acetylcholinesterase (AChE) activity in the cerebrospinal fluid (CSF) of volunteers and to test the hypothesis that rivastigmine (ENA-713; Exelon, Novartis Pharma AG, Basel, Switzerland) selectively inhibits AChE in CSF in humans at a dose producing minimal inhibition of the peripheral enzyme. Lumbar CSF samples were collected continuously (0.1 mL x min(-1)) for 49 hours from eight healthy volunteers who took either placebo or a single oral dose of rivastigmine (3 mg). CSF specimens and samples of blood cells and blood plasma were analyzed at intervals for rivastigmine and its metabolite NAP 226-90 ([-] [3-([1-dimethylaminolethyl)-phenol]), erythrocyte AChE activity, CSF AChE activity, and plasma and CSF butyrylcholinesterase (BuChE) activity. Safety evaluations were performed 23 hours after drug dosing and at the end of the study. Evaluable data were obtained from six subjects. The mean time to maximal rivastigmine plasma concentration (tmax) was 0.83 +/- 0.26 hours, the mean maximal plasma concentration (Cmax) was 4.88 +/- 3.82 ng x mL(-1), the mean plasma area under the concentration versus time curve (AUC0-infinity) was 7.43 +/- 4.74 ng x hr x mL(-1), and the mean plasma t1/2 was 0.85 +/- 0.115 hours. The concentration of rivastigmine in CSF was lower than the quantification limit for assay (0.65 ng x mL(-1)), but NAP 226-90 reached a mean Cmax of 3.14 +/- 0.57 ng x mL(-1). Only minimal inhibition of erythrocyte AChE activity (approximately 3%) was observed. Inhibition of AChE in the CSF after rivastigmine administration was significantly greater than after placebo for up to 8.4 hours after the dose and was maximal (40%) at 2.4 hours. Plasma BuChE activity was significantly lower after rivastigmine than after placebo, but this was not clinically relevant. BuChE activity in CSF was significantly lower after rivastigmine than after placebo for up to 3.6 hours after dosing, but this difference was not sustained. This study confirms the feasibility of using continuous measurement of AChE activity in CSF over prolonged periods, that rivastigmine markedly inhibits CSF AChE after a single oral dose of 3 mg, and that the inhibition of central AChE is substantially greater than that of peripheral AChE or BuChE.
Assuntos
Acetilcolinesterase/efeitos dos fármacos , Carbamatos/farmacologia , Inibidores da Colinesterase/farmacologia , Fenilcarbamatos , Acetilcolinesterase/sangue , Acetilcolinesterase/líquido cefalorraquidiano , Adolescente , Adulto , Doença de Alzheimer/tratamento farmacológico , Butirilcolinesterase , Carbamatos/metabolismo , Inibidores da Colinesterase/metabolismo , Estudos de Viabilidade , Humanos , Masculino , RivastigminaRESUMO
INTRODUCTION: This study evaluates the activity of SDZ ENA 713, a centrally-selective acetylcholinesterase (AChE) inhibitor, in the cerebral spinal fluid (CSF) of patients with Alzheimer's disease (AD), and its relationship to central and peripheral pharmacokinetic parameters. METHODS: Eighteen AD patients were enrolled in this open-label, multiple-dose study. Patients were titrated in 1 mg bid/week increments to target doses of 1, 2, 3, 4, 5, or 6 mg bid SDZ ENA 713. After patients had been maintained at their target dose for at least 3 days, continuous CSF samples were obtained via a lumbar catheter for 12.5 h, beginning 0.5 h prior to the final dose of SDZ ENA 713. RESULTS: Dose-dependent inhibition of CSF AChE was significantly correlated (P < 0.05) with plasma drug and metabolite concentrations. The 6 mg bid treatment group showed a maximum mean inhibition of 62% at 5.6 h post-dose. CONCLUSION: Rapid, sustained, dose-dependent inhibition of CSF AChE suggests that SDZ ENA 713 has therapeutic potential in AD patients.