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Review

Modulation of Urate Transport by Drugs

1
Solvo Biotechnology, Science Park, Building B2, 4-20 Irinyi József utca, H-1117 Budapest, Hungary
2
Faculty of Information Technology and Bionics, Pázmány Péter Catholic University, H-1083 Budapest, Hungary
3
Department of Morphology and Physiology, Faculty of Health Sciences, Semmelweis University, H-1088 Budapest, Hungary
*
Author to whom correspondence should be addressed.
Academic Editor: Gert Fricker
Pharmaceutics 2021, 13(6), 899; https://doi.org/10.3390/pharmaceutics13060899
Received: 19 May 2021 / Revised: 13 June 2021 / Accepted: 14 June 2021 / Published: 17 June 2021
(This article belongs to the Special Issue Drug Delivery across Physiological Barriers)
Background: Serum urate (SU) levels in primates are extraordinarily high among mammals. Urate is a Janus-faced molecule that acts physiologically as a protective antioxidant but provokes inflammation and gout when it precipitates at high concentrations. Transporters play crucial roles in urate disposition, and drugs that interact with urate transporters either by intention or by accident may modulate SU levels. We examined whether in vitro transporter interaction studies may clarify and predict such effects. Methods: Transporter interaction profiles of clinically proven urate-lowering (uricosuric) and hyperuricemic drugs were compiled from the literature, and the predictive value of in vitro-derived cut-offs like Cmax/IC50 on the in vivo outcome (clinically relevant decrease or increase of SU) was assessed. Results: Interaction with the major reabsorptive urate transporter URAT1 appears to be dominant over interactions with secretory transporters in determining the net effect of a drug on SU levels. In vitro inhibition interpreted using the recommended cut-offs is useful at predicting the clinical outcome. Conclusions: In vitro safety assessments regarding urate transport should be done early in drug development to identify candidates at risk of causing major imbalances. Attention should be paid both to the inhibition of secretory transporters and inhibition or trans-stimulation of reabsorptive transporters, especially URAT1. View Full-Text
Keywords: urate; drug-transporter interactions; in vitro prediction; hyperuricemia; hypouricemia urate; drug-transporter interactions; in vitro prediction; hyperuricemia; hypouricemia
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MDPI and ACS Style

Tátrai, P.; Erdő, F.; Dörnyei, G.; Krajcsi, P. Modulation of Urate Transport by Drugs. Pharmaceutics 2021, 13, 899. https://doi.org/10.3390/pharmaceutics13060899

AMA Style

Tátrai P, Erdő F, Dörnyei G, Krajcsi P. Modulation of Urate Transport by Drugs. Pharmaceutics. 2021; 13(6):899. https://doi.org/10.3390/pharmaceutics13060899

Chicago/Turabian Style

Tátrai, Péter, Franciska Erdő, Gabriella Dörnyei, and Péter Krajcsi. 2021. "Modulation of Urate Transport by Drugs" Pharmaceutics 13, no. 6: 899. https://doi.org/10.3390/pharmaceutics13060899

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