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Relation Between Clinical Efficacy and Pharmacokinetic Parameters After Sublingual Apomorphine in Parkinson's Disease

Durif F.; Paire, M.; Deffond, D.; Eschalier, A.; Dordain, G.; Tournilhac, M.; Lavarenne, J.
Clinical Neuropharmacology: April 1993
Original Contribution: PDF Only


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.

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