B01AC21 - Treprostinil |
Propably not porphyrinogenic |
PNP |
Rationale
Treprostinil do not inhibit or induce CYP enzymes and is therefore probably not porphyrinogenic. Side effects that can be potentially porphyrinogenic through reduction in carbohydrate intake are diarrhoea and nausea.
Chemical description
Prostacyclin analogue
Therapeutic characteristics
Treprostinil is indicated for the treatment of idiopathic or familiar pulmonary hypertension.
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 diarrhoea and nausea.
Hepatic exposure
Insignificant
Metabolism and pharmacokinetics
Treprostinil is metabolized by CYP2C8 with minor contribution by CYP2C9 (Gotzkowsky 2010). It is 91% bound to plasma proteins (Skoro-Sajer 2008). The elimination half-life is 1.3-4.6 hours.
An in vitro study has shown that treprostinil does not inhibit human hepatic microsomal CYP450 isoenzymes (CYP1A2, CYP2C9, CYP2C19, CYP2D6, CYP2E1 and CYP3A) (SPC). The Summary of Product Characteristics (SPC) also states that treprostinil is not an inducer of CYP1A, CYP2B and CYP3A.
The data from an in vivo study showed that treprostinil had no effect on warfarin (a substrate of CYP2C8 and CYP2C9 amongst others) and this indicates that treprostinil do not induce or inhibit CYP2C8 and CYP2C9 (Wade 2003).
References
- Scientific articles
- Gotzkowsky SK, Dingemanse J, et al. Lack of a pharmacokinetic interaction between oral treprostinil and bosentan in healthy adult volunteers. J Clin Pharmacol. 2010 Jul;50(7):829-34. PMID 20133511. #4369
- Skoro-Sajer N and Lang I. Treprostinil for the treatment of pulmonary hypertension. Expert Opin Pharmacother. 2008 Jun;9(8):1415-20. PMID 18473715. #1170
- Wade M, Hunt TL, Lai AA. Effect of continuous subcutaneous treprostinil therapy on the pharmacodynamics and pharmacokinetics of warfarin. J Cardiovasc Pharmacol. 2003 Jun;41(6):908-15. #1171
- Summary of Product Characteristics
- Norwegian medicines agency. Summary of Product Characteristics (SPC). (treprostinil). #1169
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