P536 Thiopurine metabolite levels in pregnant IBD patients and infants following intrauterine thiopurine exposure. (25th January 2019)

• Record Type: Journal Article
• Authors: Flanagan, E; Ross, A; Hamilton, A L; Bell, S J
• Is Part Of: Journal of Crohn's and colitis. Volume 13(2019)Supplement 1
• Page Start: S381
• Page End: S382
• Publication Date: 2019-01-25
• Subjects: Inflammatory bowel diseases -- Periodicals; 616.344005
• DOI: 10.1093/ecco-jcc/jjy222.660
• Languages: English
• ISSNs: 1873-9946

Abstract

Abstract: Background: Data regarding the pharmacokinetic effects of pregnancy on thiopurine metabolism and infant exposure to thiopurine metabolites is very limited. Data on 30 women suggested that maternal 6-thioguanine nucleotide (6-TGN) levels decreased in pregnancy, while infant 6-TGN correlated with maternal 6-TGN[1]. 6-methylmercaptopurine (6-MMP) was undetected in infants (lower limit of detection 100 pmol/8 × 10 8 RBCs). 1 We aimed to measure thiopurine metabolites in each trimester and in infants at delivery. Methods: Female patients with IBD on a thiopurine and pregnant or planning pregnancy were enrolled. Thiopurine metabolites were measured pre-conception when possible, in each trimester of pregnancy, at delivery and post-partum. Participants were offered thiopurine metabolite testing in the umbilical cord at delivery. The Wilcoxon signed-rank test was used to compare medians. Results: 22 patients were included with at least two measurements on stable dosing. Patient characteristics and metabolite levels are shown in Table 1. Median 6-TGN levels were lower during pregnancy than pre-conception and post-partum (Figure 1). Two patients required dose increases during pregnancy (levels post dose change not included). No significant difference was found between median 6-MMP levels. All patients to date (16/22) delivered babies at term with normal birth weight and no congenital anomalies. Thiopurine metabolite levels are available in five infants. In two infants, whose mothers were on low-dose thiopurine as co-therapy with anti-TNF, 6-TGNs were undetectable. One had undetectable 6-MMP, and one had 6-MMP of 27 pmol/8 × 10 8 RBCs. In the other three infants, both 6-MMP and 6-TGN were detected but were lower than maternal levels. One of these infants had a mild thrombocytopenia 102 × 10 9 /l, which resolved (6-TGN 70 pmol/8 × 10 8 RBCs). Conclusions: Thiopurine pharmacokinetics appear to be altered in pregnancy. Our preliminary results confirm 6-TGN levels may decrease in pregnancy. Infants can be exposed to both 6-TGN and 6-MMP, although at low levels. Improved knowledge of the metabolism of these drugs in pregnancy is imperative to inform dosing. Reference 1. Jharap B, de Boer NK, Stokkers et al . Intrauterine exposure and pharmacology of conventional thiopurine therapy in pregnant patients with inflammatory bowel disease. Gut 2014;63:451–7.