In the treatment of patients with
Parkinson's disease,
apomorphine has an established place as a back-up
therapy if other antiparkinsonian drugs, such as
levodopa and oral
dopamine agonists, have not controlled the existing response fluctuations.
Apomorphine is a synthetic derivative of
morphine, with a totally distinct pharmacological profile. It is a very lipophilic compound which is easily (auto)oxidised. This (auto)oxidation is the main metabolic route besides glucuronidation and sulphation, which are both responsible for about 10% of the metabolic transformation.
Apomorphine quickly passes the nasal and intestinal mucosa as well as the blood-brain barrier (depending on the administration route). Many routes of administration have been explored, but subcutaneous, sublingual, nasal and
rectal administration are used in clinical practice. The volume of distribution varies between 1 and 2 times bodyweight. The elimination half-life is very short (30 to 90 min) depending on the type of parenteral administration.
Apomorphine is a high clearance
drug (3 to 5 L/kg/h) and is mainly excreted and metabolised by the liver. Only 3 to 4% is excreted unchanged in the urine. The clinical effect of
apomorphine can be linked directly to its concentration in the cerebrospinal fluid. Consequently, a 2-compartment model can be used to predict the clinical effects of
apomorphine. The pharmacokinetic-pharmacodynamic data reflect the clinical observations of steep dose-effect curves if
apomorphine is used in patients with random 'on-off' fluctuations. These dose-effect curves are less steep in stable or 'wearing-off' (end-of-dose deterioration) patients.
Intravenous infusions of
apomorphine in combination with timed motor assessments can be used clinically to characterise the therapeutic window of a particular patient if
dyskinesia persists after single
injections of
apomorphine. If more population data become available, the population pharmacokinetics-pharmacodynamics of
apomorphine could be helpful in predicting the clinical effects of
apomorphine in the several subgroups of patients with
Parkinson's disease.