Pazopanib is a major substrate of CYP3A4. It is a weak inhibitor of CYP3A4 in vivo. Risk for gastrointestinal adverse events in the form of nausea and diarrhoea motivates vigilance against insufficient intake of food, especially of carbohydrate.

The sulphonamide moiety of the molecule is not directly coupled to a heterocycle, but to aminobenzene and this molecule is probably not porphyrinogenic.

Pazopanib is indicated for advanced kidney cell cancer. 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 nausea, vomiting, diarrhoea and abdominal pain.

Significant

Pazopanib is highly protein bound (> 99%) and is metabolized mainly by CYP3A4 with minor metabolism by CYP1A2 and CYP2C8. It is a weak inhibitor of CYP3A4, CYP2C8 and CYP2D6 (Keisner 2011, Tan 2010). The half-life elimination is approximately 31 hours. In vitro studies have shown that pazopanib inhibit CYP1A2, 3A4, 2B6, 2C8, 2C9, 2C19 and 2E1, and induce CYP3A4 (SPC). Clinical studies with caffeine, a CYP1A2 substrate, and omeprazole, a CYP2C19 substrate, showed that pazopanib had no relevant effect on the pharmacokinetics of the substrates (SPC). This indicates that pazopanib does not induce or inhibit CYP1A2 or CYP2C19. An in vivo study has shown that co-administration of pazopanib with paclitaxtel, a CYP3A4 and CYP2C8 substrate, increased the plasma concentration of paclitaxel by 26%. This indicates that pazopanib may be a weak inhibitor of CYP3A4 or CYP2C8, or both (SPC, Tan 2010 and van Geel 2012). Pazopanib also increased the mean AUC of midazolam, a CYP3A4 substrate, by 30% which indicates that it is an inhibitor of CYP3A4 (SPC). In vitro data indicates that pazopanib is a mechanism-based inhibitor of CYP3A4 (Kenny 2012).