1. Misoprostol-induced fever and genetic polymorphisms in drug transporters SLCO1B1 and ABCC4 in women of Latin American and European ancestry.
- Author
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Alfirevic A, Durocher J, Elati A, León W, Dickens D, Rädisch S, Box H, Siccardi M, Curley P, Xinarianos G, Ardeshana A, Owen A, Zhang JE, Pirmohamed M, Alfirevic Z, Weeks A, and Winikoff B
- Subjects
- Abortifacient Agents, Nonsteroidal metabolism, Adult, Blood-Brain Barrier metabolism, Body Temperature, Cell Line, Female, Genetic Predisposition to Disease, Genotype, Humans, Latin America, Liver-Specific Organic Anion Transporter 1, Misoprostol metabolism, Polymorphism, Single Nucleotide genetics, Postoperative Hemorrhage complications, Postoperative Hemorrhage drug therapy, Postoperative Hemorrhage genetics, Pregnancy, White People, Abortifacient Agents, Nonsteroidal adverse effects, Fever chemically induced, Fever genetics, Misoprostol adverse effects, Multidrug Resistance-Associated Proteins genetics, Organic Anion Transporters genetics, Polymorphism, Genetic genetics
- Abstract
Aim: Misoprostol, a prostaglandin analogue used for the treatment of postpartum hemorrhage and termination of pregnancy, can cause high fevers. Genetic susceptibility may play a role in misoprostol-induced fever., Subjects & Methods: Body temperature of women treated with misoprostol for termination of pregnancy in the UK (n = 107) and for postpartum hemorrhage in Ecuador (n = 50) was measured. Genotyping for 33 single nucleotide polymorphisms in 15 candidate genes was performed. Additionally, we investigated the transport of radiolabeled misoprostol acid across biological membranes in vitro., Results: The ABCC4 single nucleotide polymorphism rs11568658 was associated with misoprostol-induced fever. Misoprostol acid was transported across a blood-brain barrier model by MRP4 and SLCO1B1., Conclusion: Genetic variability in ABCC4 may contribute to misoprostol-induced fever in pregnant women. Original submitted 21 January 2015; Revision submitted 24 April 2015.
- Published
- 2015
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