Intravenous apomorphine therapy in Parkinson's disease - Clinical and pharmacokinetic observations

Citation
Aj. Manson et al., Intravenous apomorphine therapy in Parkinson's disease - Clinical and pharmacokinetic observations, BRAIN, 124, 2001, pp. 331-340
Citations number
53
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Neurology,"Neurosciences & Behavoir
Journal title
BRAIN
ISSN journal
0006-8950 → ACNP
Volume
124
Year of publication
2001
Part
2
Pages
331 - 340
Database
ISI
SICI code
0006-8950(200102)124:<331:IATIPD>2.0.ZU;2-K
Abstract
Six patients with Parkinson's disease and refractory motor fluctuations, wi th severe subcutaneous (s,c,) nodule formation as a result of long-term s,c , apomorphine infusions, were switched to intravenous (i,v,) therapy via a long-term in-dwelling venous catheter, Five patients were followed-up for a mean of 7 months (range 0,5-18 months). All patients had plasma apomorphin e concentrations measured at baseline during s,c, infusions and three had f ollow-up measurements when stabilized on i,v, therapy, to test the hypothes is that motor fluctuations in these patients are largely due to impaired ab sorption of apomorphine, The mean i,v, rate of 9.0 mg/h (range 5-14 mg) and 24-h dose of 256.7 mg (range 90-456 mg) of apomorphine were not significan tly reduced compared with the s,c, route (9.24 mg/h and 243.4 mg), However, additional oral anti-parkinsonian medication was reduced by a mean of 59%, and 'off' time was virtually eliminated (mean reduction from 5.4 to 0.5 h per day, P < 0,05), There was also a significant reduction in dyskinesias a nd markedly improved quality of life. Pharmacokinetic analysis demonstrated more reliable and smoother delivery of apomorphine via the i,v, route, alt hough 'off' periods were not always explained by low plasma apomorphine con centrations. Complication rates were high and included three unforeseen haz ardous intravascular thrombotic complications, secondary to apomorphine cry stal accumulation, necessitating cardiothoracic surgery. We conclude that i ,v, apomorphine therapy holds promise as a more effective way of controllin g motor fluctuations than the s,c, route. However, further preclinical rese arch is required before i,v, Britaject apomorphine can be recommended for r outine clinical practice. Even when stable plasma apomorphine concentration s were achieved, motor fluctuations could not be totally eradicated, sugges ting that postsynaptic receptor changes may also play a role in the refract ory 'off' periods in these patients.