Hydrochlorothiazide: Hydrochlorothiazide is not metabolized by CYP enzymes and does not induce or inhibit these enzymes. It is therefore regarded as probably not porphyrinogenic. Eprosartan: Eprosartan is not metabolized by CYP enzymes, and is found not to be an inhibitor of CYP, there are no indications that eprosartan has potential for CYP induction.

Hydrochlorothiazide: Sulfonamide congener. Eprosartan: Angiotensin II receptor antagonist

Hydrochlorothiazide: Hydrochlorothiazide is a thiazide diuretic that inhibits reabsorption of electrolytes in the distal tubule, leading to increased excretion of water, sodium, chloride, potassium, magnesium and other electrolytes. It is administered orally. Eprosartan: Eprosartan is used in the treatment of essential hypertension. It is administered orally.

Hydrochlorothiazide: Hydrocholorothiazide is not metabolized, but is eliminated mainly unchanged in the urine. The plasma half-life is about 9,4 – 13 hours (Beermann 1976, Drugbank, SPC). Eprosartan: Eprosartan is not metabolized by CYP, but is eliminated by biliary and renal excretion, primarily as unchanged compound. Less than 2 per cent is excreted as a glucuronide (drugbank). Eprosartan has been shown not to inhibit human cytochrome P450 enzymes CYP1A, 2A6, 2C9/8, 2C19, 2D6, 2E and 3A in vitro in concentrations up to 100µM. This concentration is approximately 15- fold higher than the mean maximum plasma concentration after administration of eprosatran 1200 mg a day for 7 days (SPC, Taavitsainen 2000). In an in vivo drug-drug interaction study eprosartan did not alter the plasma concentration of CYP substrates (Blum 1999). It has an elimination half-life of 5-9 hours (SPC).

Hydrochlorothiazide: In an in ovo study of chick embryo livers, methyclothiazide, another thiazide drug, was found to have potential for induction of ALAS, whereas hydroclorothiazide and other thiazides was found not to have these effects (Anderson 1981). The results from these types of animal studies are not directly transferable to human, and cannot be given weight in the judgement of porphyrinogeniciry of drugs (Hift 2011).

Hydrochlorothiazide: Thunell, patient report (n=1): tolerated. Andersson, patient reports (n=10): tolerated. Peters: On basis of clinical experience probably not porphyrinogenic.

Hydrochlorothiazide: Uneventful use reported in 9 patients with acute porphyria. Eprosartan: Uneventful use reported in 1 patient with acute porphyria.