N04BC07 - Apomorphine |
Propably not porphyrinogenic |
PNP |
Rationale
Essentially non-Cyp metabolized morphine derivative very rapidly cleared (< 1 h) from the circulation. Pharmacokinetic Cyp-dependent drug interactions with apomorphine as perpetrator are unlikely.
Potentially porphyrogenic nausea and vomiting may prevented by careful antiemetic premedication by domperidone. Dopamine-antagonistic phenothiazine antiemetics or metoclopramide are not to be used.
Chemical description
Dibenzokinoline morphine derivative with structural similarities to dopamine. Administered as the hydrochloride.
Therapeutic characteristics
Apomorphine is used in the acute treatment of motoric off-periods in MbParkinson. Administered after thorough antiemetic premedication. Administered acutely during hypokinetic (motoric off)-period of Mb parkinson. Administered subcutaneously due to poor oral bioavailability as it undergoes extensive first pass metabolism. Only to be used in in-hospital care in the hands of specialists. Apomorphine stimulates dopaminergic postsynaptic receptor sites by way of dopamine receptor D1 and D2 agonism.
Physiological effects of possible relevance to acute porphyria: results from in vitro tests suggests that apomorphine may influence the secretion of pituitary hormones which may in turn have an effect on the regulation of CYP enzymes, but the clinical relevance is uncertain.
Metabolism and pharmakokinetics
Well absorbed after s.c. injection, with rapid (4-12 min) onset of action, and short (1 h) duration of effect. The only recognized clearance pathway is renal excretion after glucuronidation and sulphonation. In vitro studies have shown inhibition of CYP1A2, 2D6 and 3A4, but only for concentrations well above clinical relevance.
References
- Scientific articles
- Argiolas A, Hedlund H, et al. The pharmacology and clinical pharmacokinetics of apomorphine SL. BJU Int. 2001 Oct;88 Suppl 3:18-21. #2615
- Wójcikowski J, Daniel WA, et al. The role of the nervous system in the regulation of liver cytochrome p450. Curr Drug Metab. 2011 Feb;12(2):124-38. #2618
- Drug reference publications
- Sweetman SC, editor. Martindale: The complete drug reference. Apomorphine (19.06.2012). #2616
- Summary of Product Characteristics
- The electronic Medicines Compendium (emc). Summary of Product Characteristics (SPC). Apomorphine. #2617
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