Apomorphine pharmacokinetics in Parkinsonism after intranasal and subcutaneous application

Abstract

Apomorphine was administered subcutaneously and intranasally to 7 patients suffering from Parkinsonism with 'on-off' problems. This comparative pharmacokinetic study showed that the two routes of administration are comparable with respect to absorption kinetics. Apomorphine is rapidly absorbed when administered intranasally or subcutaneously with an absorption half life of 8.6 min and 5.8 min, respectively. The high rate of absorption is also reflected by the time for the plasma concentration to peak (tmax) and the lag times. The tmax was 23 min for intranasal route and 18 min for the subcutaneous route while the lag times were 2.8 min and 3.9 min, respectively. The bioavailability of intranasal apomorphine compared to the subcutaneous route amounted to 45%. After intranasal and subcutaneous administrations, the elimination half life of apomorphine amounted to 31 min and 27 min, respectively.

Free radical scavenging properties of apomorphine enantiomers and dopamine: Possible implication in their mechanism of action in parkinsonism

“…(Sam et al, 1995;Gancher et al, 1989). These results could suggest that in the body most of the apomorphine undergoes autoxidation and therefore acting as a strong antioxidant.…”

Apomorphine protects against MPTP-induced neurotoxicity in mice

“…19 The relatively high doses (5 and 10 mg/kg) of APO used in this study to achieve neuroprotection relates to the pharmacokinetically unstable and readily oxidizable nature of APO. 34,35 The neuroprotective effect achieved by 5 and 10 mg/kg of APO against the loss of neuronal TH is reflected by the almost normalized levels of DA. This restoration could result from an increase in DA synthesis caused by an elevation in the activity of TH, the rate-limiting enzyme, or from a decrease in the turnover of DA.…”

Betamethasone does not prevent nausea and vomiting induced by the dopamine-agonist apomorphine

“…The effects of apomorphine started within ten minutes and the duration was short, confirming results from previous studies. 10,11 Betamethasone 8 mg iv could not abolish the apomorphine-induced emesis, and consequently, given 15 min before apomorphine, does not demonstrate dopamine-antagonistic effects.…”

“…The elimination half-life is about 30 min. 10,11 The antidiuretic hormone arginine vasopressin is released during apomorphine-induced emesis. Metoclopramide is a procaine amide derivate and a benzamide prokinetic agent with dual sites of action, blocking D 2 -receptors both in the CTZ and the gastrointestinal tract.…”