Pharmacokinetics of apomorphine in parkinsonian patients
Identifieur interne : 002523 ( Main/Exploration ); précédent : 002522; suivant : 002524Pharmacokinetics of apomorphine in parkinsonian patients
Auteurs : E. Nicolle [France] ; Pierre Pollak [France] ; F. Serre-Debeauvais [France] ; P. Richard [France] ; Cl Gervason [France] ; E. Broussolle [France] ; M. Gavend [France]Source :
- Fundamental & Clinical Pharmacology [ 0767-3981 ] ; 1993-07.
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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.
Url:
DOI: 10.1111/j.1472-8206.1993.tb00238.x
Affiliations:
- France
- Auvergne-Rhône-Alpes, Rhône-Alpes
- Grenoble, Lyon
- Centre hospitalier universitaire Grenoble Alpes
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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.</div></front></TEI><affiliations><list><country><li>France</li></country><region><li>Auvergne-Rhône-Alpes</li><li>Rhône-Alpes</li></region><settlement><li>Grenoble</li><li>Lyon</li></settlement><orgName><li>Centre hospitalier universitaire Grenoble Alpes</li></orgName></list><tree><country name="France"><region name="Auvergne-Rhône-Alpes"><name sortKey="Nicolle, E" sort="Nicolle, E" uniqKey="Nicolle E" first="E." last="Nicolle">E. Nicolle</name></region><name sortKey="Broussolle, E" sort="Broussolle, E" uniqKey="Broussolle E" first="E." last="Broussolle">E. Broussolle</name><name sortKey="Gavend, M" sort="Gavend, M" uniqKey="Gavend M" first="M." last="Gavend">M. Gavend</name><name sortKey="Gervason, Cl" sort="Gervason, Cl" uniqKey="Gervason C" first="Cl" last="Gervason">Cl Gervason</name><name sortKey="Pollak, P" sort="Pollak, P" uniqKey="Pollak P" first="P." last="Pollak">Pierre Pollak</name><name sortKey="Richard, P" sort="Richard, P" uniqKey="Richard P" first="P." last="Richard">P. Richard</name><name sortKey="Serre Ebeauvais, F" sort="Serre Ebeauvais, F" uniqKey="Serre Ebeauvais F" first="F." last="Serre-Debeauvais">F. Serre-Debeauvais</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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