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Misoprostol-induced fever and genetic polymorphisms in drug transporters

Published:
Jun. 2015
Type:
Staff Publication
Topic:
Postpartum Hemorrhage
Authors:
Durocher, Jill, Winikoff, Beverly Alfirevic, A., Durocher, J., Elati, A., León, W., Dickens, D., Rädisch, S., Box, H., Siccardi, M., Curley, P., Xinarianos, G., A

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.

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