endocrine and metabolic disorders
Overview of Porphyrias
Secondary Porphyrinuria
Several diseases unrelated to porphyrias may involve increased urinary excretion of porphyrins; this phenomenon is described as secondary porphyrinuria. , among others ( Secondary porphyrinuria references ). Such medications may also lead to an increase in urinary porphyrin excretion. Uroporphyrin may also be elevated in patients with hepatobiliary disorders. Protoporphyrin is not excreted in urine because it is water insoluble. Disorders that cause secondary porphyrinuria (as well as disorders that cause clinical syndromes mimicking acute porphyrias) typically do not elevate urinary levels of ALA and PBG, so normal levels of ALA and PBG help distinguish secondary porphyrinuria from acute porphyrias. However, some patients with Lead Poisoning can have elevated urinary ALA levels. Blood lead levels should be measured in such patients. If urinary ALA and PBG are normal or only slightly increased, measurement of urinary total porphyrins and high-performance liquid chromatography profiles of these porphyrins are helpful for differential diagnosis of acute porphyric syndromes. Coproporphyrin (CP) I and III and other biomarkers may be useful as selective and sensitive biomarkers for certain drug–drug interactions ( Secondary porphyrinuria references ). In addition, CP I and III are potential biomarkers that can track nonalcoholic steatohepatitis (NASH) progression ( 1.An G, Wang X, Morris ME: Flavonoids are inhibitors of human organic anion transporter 1 (OAT1)-mediated transport.Drug Metab Dispos42(9):1357–1366, 2014. doi: 10.1124/dmd.114.059337 2.Duan P, Li S, Ni A, et al: Potent inhibitors of human organic anion transporters 1 and 3 from clinical drug libraries: Discovery and molecular characterization.Mol Pharm9(11):3340–3346, 2012. doi: 10.1021/mp300365t 3.Barnett S, Ogungbenro K, Ménochet K, et al: Comprehensive evaluation of the utility of 20 endogenous molecules as biomarkers of OATP1B inhibition compared withrosuvastatinand coproporphyrin I.J Pharmacol Exp Ther368(1):125–135, 2019. doi:10.1124/jpet.118.253062 4.Barnett S, Ogungbenro K, Ménochet K, et al: Gaining mechanistic insight into coproporphyrin I as endogenous biomarker for OATP1B-mediated drug-drug interactions using population pharmacokinetic modeling and simulation.Clin Pharmacol Ther104(3):564–574, 2018. doi:10.1002/cpt.983 5.Kunze A, Ediage EN, Dillen L, et al: Clinical investigation of coproporphyrins as sensitive biomarkers to predict mild to strong OATP1B-mediated drug-drug interactions.Clin Pharmacokinet57(12):1559–1570, 2018. doi:10.1007/s40262-018-0648-3 6.Shen H, Christopher L, Lai Y, et al: Further studies to support the use of coproporphyrin I and III as novel clinical biomarkers for evaluating the potential for organic anion transporting polypeptide 1B1 and OATP1B3 inhibition.Drug Metab Dispos46(8):1075–1082, 2018. doi:10.1124/dmd.118.081125 7.Chatterjee S, Mukherjee S, Sankara Sivaprasad LVJ, et al: Transporter activity changes in nonalcoholic steatohepatitis: Assessment with plasma coproporphyrin I and III.J Pharmacol Exp Ther376(1):29–39, 2021. doi:10.1124/jpet.120.000291 