Misoprostol-induced fever and genetic polymorphisms in drug transporters SLCO1B1 and ABCC4 in women of Latin American and European ancestry
- June 30th, 2015
- Postpartum Hemorrhage
- 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, J.E., Pirmohamed, M., Alfirevic, Z., Weeks, A., Winikoff, B.
Pharmacogenomics; June 30, 2015; 16(9):919-28; doi:10.2217/pgs.15.53
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.