N04BC04 - Ropinirole |
Propably not porphyrinogenic |
PNP |
Rationale
Ropinirole is not an inhibitor or inducer of CYP1A2 or other CYP enzymes in vivo.
Risk for gastrointestinal adverse events in the form of vomiting and nausea motivates vigilance against insufficient intake of food, especially of carbohydrate.
Therapeutic characteristics
Ropinirole is indicated for the treatment of restless legs syndrome and Parkinsons.
Very common side effects that can be potentially porphyrinogenic through reduction in carbohydrate intake and that also can be confused with an acute porphyria attack are vomiting and nausea. Other common side effects are abdominal pain, fatigue, syncope, somnolence and dizziness.
In the low doses employed there are no side effects pointing to engagement of the stress-activated dopamine pathways that give rise to porphyrinogenic glucagon-signaling and cortisone-release.
Hepatic exposure
Insignificant.
Metabolism and pharmakokinetics
Ropinirole is metabolised mainly by CYP1A2 (Kaye 2000 and SPC) with minor contribution by CYP3A. Only 10% is excreted as unchanged drug (Kaye 2000). Half-life elimination is 6 hours.
In vitro studies have shown that ropinirole is a potent inhibitor of CYP2D6 and a less potent inhibitor of CYP1A2 (Kvernmo 2006). However, in vitro data also indicate that ropinirole has low potential to inhibit CYP450 enzymes at therapeutic doses (SPC).
Ropinirole did not change the pharmacokinetics of theophylline, a CYP1A2 substrate, when co-administrated (SPC and Thalamas 1999). This indicates that ropinirole is not an inhibitor or an inducer of CYP1A2.
Plasma concentrations of ropinirole are unlikely to exceed 0.01 µM (Bloomer 1997 and Boothman 1990) which makes it unlikely that ropinirole will activate PXR and induce CYP enzymes.
Personal communication
Thunell, clinical observation (n=1): tolerated.
IPNet drug reports
Uneventful use reported in 1 patient with acute porphyria.
References
- Scientific articles
- Bloomer JC, Clarke SE, Chenery RJ. In vitro identification of the P450 enzymes responsible for the metabolism of ropinirole. Drug Metab Dispos. 1997 Jul;25(7):840-4. #2609
- Boothman BR, Spokes EG. Pharmacokinetic data for ropinirole. Lancet. 1990 Sep 29;336(8718):814. #2610
- Kaye CM, Nicholls B. Clinical pharmacokinetics of ropinirole. Clin Pharmacokinet. 2000 Oct;39(4):243-54. PMID 11069211. #2611
- Kvernmo T, Härtter S, Burger E. A review of the receptor-binding and pharmacokinetic properties of dopamine agonists. Clin Ther. 2006 Aug;28(8):1065-78. PMID 16982285. #2612
- Thalamas C, Taylor A, et al. Lack of pharmacokinetic interaction between ropinirole and theophylline in patients with Parkinsons disease. Eur J Clin Pharmacol. 1999 Jun;55(4):299-303. #2614
- Summary of Product Characteristics
- Norwegian medicines agency. Summary of Product Characteristics (SPC). Ropinirol. #2613
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