Subcutaneously administered apomorphine: pharmacokinetics and metabolism.
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LeWitt PA
Subcutaneously administered apomorphine: pharmacokinetics and metabolism.
Neurology. 2004 Mar 23;62(6 Suppl 4):S8-11. doi: 10.1212/wnl.62.6_suppl_4.s8.
- PubMed ID
- 15037665 [ View in PubMed]
- 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 T(max)lags behind plasma T(max) by 10 to 20 minutes. Considerable intersubject variability is found with pharmacokinetic variables; in some studies there are five- to tenfold differences in C(max)and 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.
DrugBank Data that Cites this Article
- Drugs
- Drug Targets
Drug Target Kind Organism Pharmacological Action Actions Apomorphine 5-hydroxytryptamine receptor 1A Protein Humans UnknownAgonistDetails Apomorphine 5-hydroxytryptamine receptor 2A Protein Humans UnknownAgonistDetails Apomorphine 5-hydroxytryptamine receptor 2B Protein Humans UnknownAgonistDetails Apomorphine 5-hydroxytryptamine receptor 2C Protein Humans UnknownAgonistDetails Apomorphine Dopamine D1 receptor Protein Humans UnknownAgonistDetails Apomorphine Dopamine D2 receptor Protein Humans YesAgonistDetails Apomorphine Dopamine D3 receptor Protein Humans YesAgonistDetails Apomorphine Dopamine D4 receptor Protein Humans YesAgonistDetails Apomorphine Dopamine D5 receptor Protein Humans UnknownAgonistDetails