首页 | 本学科首页   官方微博 | 高级检索  
     


Pharmacokinetics of apomorphine in parkinsonian patients
Authors:E. Nicolle  P. Pollak  F. Serre-Debeauvais  P. Richard  CL Gervason  E. Broussolle  and M. Gavend
Affiliation:Laboratoire de Pharmacologie, Centre Hospitalier Universitaire de Grenoble, BP 217, 38043 Grenoble Cedex 9, France;Département des Neurosciences Cliniques et Biologiques, Clinique Neurologique, Centre Hospitalier Universitaire de Grenoble, BP 217, 38043 Grenoble Cedex 9, France;Service de Neurologie, Hôpital de l'Antiquaille, 69321 Lyon Cedex 5, France
Abstract:
Summary— Apomorphine, a dopamine agonist, has been used efficiently in parkinsonian patients to treat severe levodopa-induced on-off phenomenon. Motor improvement has been obtained both with continuous subcutaneous (SC) infusions, and multiple SC injections. So as to assist in the understanding of the clinical results, we studied the peripheral pharmacokinetics of apomorphine in 20 patients after intravenous (IV) or SC injections in the anterior abdominal wall and in the thigh at various doses, or SC infusion. Plasma apomorphine levels were measured by high-performance liquid chromatography with electrochemical detection. After an SC injection in the abdominal wall, the Tmax was brief (16 ± 11 min) the drug was rapidly cleared from the plasma and had a short plasma half-life (69.7 ± 25.8 min). The AUC was similar following SC and IV injections, suggesting that apomorphine was completely absorbed from subcutaneous tissue. Inter-subject variability in drug absorption was large. We noticed a trend towards a more complete absorption following injection in the abdominal wall rather than in the thigh. In patients chronically treated by continuous SC infusion, the apparent plasma half-life was five times longer than that following SC or IV injections. These pharmacokinetic data may explain the rapid onset and brief duration of clinical effects, and the usefulness of individual titration for intermittent SC apomorphine injections, and the smoother motor response obtained with continuous SC infusions.
Keywords:apomorphine    Parkinson's disease    human pharmacokinetics    bolus injection    continuous SC infusion
设为首页 | 免责声明 | 关于勤云 | 加入收藏

Copyright©北京勤云科技发展有限公司  京ICP备09084417号