Relation between clinical efficacy and pharmacokinetic parameters after sublingual apomorphine in Parkinson's disease.
Identifieur interne : 001677 ( PubMed/Curation ); précédent : 001676; suivant : 001678Relation between clinical efficacy and pharmacokinetic parameters after sublingual apomorphine in Parkinson's disease.
Auteurs : F. Durif [France] ; M. Paire ; D. Deffond ; A. Eschalier ; G. Dordain ; M. Tournilhac ; J. LavarenneSource :
- Clinical neuropharmacology [ 0362-5664 ] ; 1993.
English descriptors
- KwdEn :
- MESH :
- chemical , administration & dosage : Apomorphine.
- chemical , pharmacokinetics : Apomorphine.
- chemical , therapeutic use : Apomorphine.
- drug therapy : Parkinson Disease.
- Administration, Sublingual, Adult, Aged, Chromatography, High Pressure Liquid, Female, Humans, Male, Middle Aged.
Abstract
Apomorphine was administered sublingually in two single doses (0.3 and 0.6 mg/kg) to seven patients with idiopathic Parkinson's disease (PD) to assess the relation between clinical efficacy, dosage, and pharmacokinetic parameters of apomorphine. On day 1 and day 3, patients were given 0.3 mg/kg and 0.6 mg/kg of apomorphine, respectively (3 mg tablets). Before apomorphine administration and during the following 4 h, motor score was assessed by measuring tremor, akinesia scores, rising from a chair, and walking speed. The delay to turn on was not different between the two doses but after the 0.3 mg/kg dose, only three patients turned on, whereas all the patients treated with 0.6 mg/kg turned on. Apomorphine (0.3 mg/kg) induced a shorter duration of the "on" period than 0.6 mg/kg (0.3 mg/kg: 24.2 +/- 14.6 min; 0.6 mg/kg: 86.7 +/- 14.9 min). The time to obtain the peak plasma concentration (tmax) obtained with the two doses were not different (0.3 mg/kg: 31.5 +/- 3.4 min; 0.6 mg/kg: 38.3 +/- 2.8 min). Peak plasma concentrations (Cmax) and areas under the curve (AUC) were significantly higher after 0.6 mg/kg than 0.3 mg/kg (Cmax: 0.3 mg/kg: 7.5 +/- 3.2 ng/ml; 0.6 mg/kg: 22.7 +/- 3.6 ng/ml; p < 0.01; AUC: 0.3 mg/kg: 929 +/- 109 ng/ml/min; 0.6 mg/kg; 2,277 +/- 209 ng/ml/min; p < 0.01). There was a significant linear correlation between the duration of therapeutic effect, AUC, and Cmax (r = 0.86, p < 0.01 for AUC; r = 0.63, p < 0.05 for Cmax). These results show that sublingual apomorphine could be of interest in the treatment of "off" phases in parkinsonian patients with motor fluctuations.
PubMed: 8477411
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<country xml:lang="fr">France</country>
<wicri:regionArea>Clinique Neurologique, Clermont-Ferrand</wicri:regionArea>
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<author><name sortKey="Paire, M" sort="Paire, M" uniqKey="Paire M" first="M" last="Paire">M. Paire</name>
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<author><name sortKey="Deffond, D" sort="Deffond, D" uniqKey="Deffond D" first="D" last="Deffond">D. Deffond</name>
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<author><name sortKey="Eschalier, A" sort="Eschalier, A" uniqKey="Eschalier A" first="A" last="Eschalier">A. Eschalier</name>
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<author><name sortKey="Dordain, G" sort="Dordain, G" uniqKey="Dordain G" first="G" last="Dordain">G. Dordain</name>
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<author><name sortKey="Tournilhac, M" sort="Tournilhac, M" uniqKey="Tournilhac M" first="M" last="Tournilhac">M. Tournilhac</name>
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<author><name sortKey="Paire, M" sort="Paire, M" uniqKey="Paire M" first="M" last="Paire">M. Paire</name>
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<author><name sortKey="Deffond, D" sort="Deffond, D" uniqKey="Deffond D" first="D" last="Deffond">D. Deffond</name>
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<term>Adult</term>
<term>Aged</term>
<term>Apomorphine (administration & dosage)</term>
<term>Apomorphine (pharmacokinetics)</term>
<term>Apomorphine (therapeutic use)</term>
<term>Chromatography, High Pressure Liquid</term>
<term>Female</term>
<term>Humans</term>
<term>Male</term>
<term>Middle Aged</term>
<term>Parkinson Disease (drug therapy)</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="administration & dosage" xml:lang="en"><term>Apomorphine</term>
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<keywords scheme="MESH" type="chemical" qualifier="therapeutic use" xml:lang="en"><term>Apomorphine</term>
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<keywords scheme="MESH" qualifier="drug therapy" xml:lang="en"><term>Parkinson Disease</term>
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<keywords scheme="MESH" xml:lang="en"><term>Administration, Sublingual</term>
<term>Adult</term>
<term>Aged</term>
<term>Chromatography, High Pressure Liquid</term>
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<front><div type="abstract" xml:lang="en">Apomorphine was administered sublingually in two single doses (0.3 and 0.6 mg/kg) to seven patients with idiopathic Parkinson's disease (PD) to assess the relation between clinical efficacy, dosage, and pharmacokinetic parameters of apomorphine. On day 1 and day 3, patients were given 0.3 mg/kg and 0.6 mg/kg of apomorphine, respectively (3 mg tablets). Before apomorphine administration and during the following 4 h, motor score was assessed by measuring tremor, akinesia scores, rising from a chair, and walking speed. The delay to turn on was not different between the two doses but after the 0.3 mg/kg dose, only three patients turned on, whereas all the patients treated with 0.6 mg/kg turned on. Apomorphine (0.3 mg/kg) induced a shorter duration of the "on" period than 0.6 mg/kg (0.3 mg/kg: 24.2 +/- 14.6 min; 0.6 mg/kg: 86.7 +/- 14.9 min). The time to obtain the peak plasma concentration (tmax) obtained with the two doses were not different (0.3 mg/kg: 31.5 +/- 3.4 min; 0.6 mg/kg: 38.3 +/- 2.8 min). Peak plasma concentrations (Cmax) and areas under the curve (AUC) were significantly higher after 0.6 mg/kg than 0.3 mg/kg (Cmax: 0.3 mg/kg: 7.5 +/- 3.2 ng/ml; 0.6 mg/kg: 22.7 +/- 3.6 ng/ml; p < 0.01; AUC: 0.3 mg/kg: 929 +/- 109 ng/ml/min; 0.6 mg/kg; 2,277 +/- 209 ng/ml/min; p < 0.01). There was a significant linear correlation between the duration of therapeutic effect, AUC, and Cmax (r = 0.86, p < 0.01 for AUC; r = 0.63, p < 0.05 for Cmax). These results show that sublingual apomorphine could be of interest in the treatment of "off" phases in parkinsonian patients with motor fluctuations.</div>
</front>
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<ArticleTitle>Relation between clinical efficacy and pharmacokinetic parameters after sublingual apomorphine in Parkinson's disease.</ArticleTitle>
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<Abstract><AbstractText>Apomorphine was administered sublingually in two single doses (0.3 and 0.6 mg/kg) to seven patients with idiopathic Parkinson's disease (PD) to assess the relation between clinical efficacy, dosage, and pharmacokinetic parameters of apomorphine. On day 1 and day 3, patients were given 0.3 mg/kg and 0.6 mg/kg of apomorphine, respectively (3 mg tablets). Before apomorphine administration and during the following 4 h, motor score was assessed by measuring tremor, akinesia scores, rising from a chair, and walking speed. The delay to turn on was not different between the two doses but after the 0.3 mg/kg dose, only three patients turned on, whereas all the patients treated with 0.6 mg/kg turned on. Apomorphine (0.3 mg/kg) induced a shorter duration of the "on" period than 0.6 mg/kg (0.3 mg/kg: 24.2 +/- 14.6 min; 0.6 mg/kg: 86.7 +/- 14.9 min). The time to obtain the peak plasma concentration (tmax) obtained with the two doses were not different (0.3 mg/kg: 31.5 +/- 3.4 min; 0.6 mg/kg: 38.3 +/- 2.8 min). Peak plasma concentrations (Cmax) and areas under the curve (AUC) were significantly higher after 0.6 mg/kg than 0.3 mg/kg (Cmax: 0.3 mg/kg: 7.5 +/- 3.2 ng/ml; 0.6 mg/kg: 22.7 +/- 3.6 ng/ml; p < 0.01; AUC: 0.3 mg/kg: 929 +/- 109 ng/ml/min; 0.6 mg/kg; 2,277 +/- 209 ng/ml/min; p < 0.01). There was a significant linear correlation between the duration of therapeutic effect, AUC, and Cmax (r = 0.86, p < 0.01 for AUC; r = 0.63, p < 0.05 for Cmax). These results show that sublingual apomorphine could be of interest in the treatment of "off" phases in parkinsonian patients with motor fluctuations.</AbstractText>
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