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Abstract
Article Abstract— Apomorphine is a non-narcotic morphine derivative that acts as a potent dopaminergic agonist. Its high first-pass hepatic metabolism prevents effectiveness by the oral route; instead, subcutaneous injection is the usual route, and intranasal, sublingual, rectal, and iontophoretic transdermal delivery has been investigated for the treatment of Parkinson’s disease (PD). The rate of uptake after subcutaneous injection is influenced by factors such as location, temperature, depth of injection, and body fat. Studies have shown the latency of onset to clinical effect after s.c. injection ranged from 7.3 to 14 minutes. Cerebrospinal fluid Tmaxlags behind plasma Tmax by 10 to 20 minutes. Considerable intersubject variability is found with pharmacokinetic variables; in some studies there are five- to tenfold differences in Cmaxand area-under-the-concentration-time-curve seen in PD patients. Apomorphine metabolism occurs through several enzymatic pathways, including N-demethylation, sulfation, glucuronidation, and catechol-O-methyltransferase as well as by nonenzymatic oxidation. The complexities of apomorphine uptake, distribution, and clearance probably contribute to its variability of clinical actions.
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