The Effect of Pregnancy and Inflammatory Bowel Disease on the Pharmacokinetics of Drugs Related to Inflammatory Bowel Disease—A Systematic Literature Review
Due to ethical and practical reasons, a knowledge gap exists on the pharmacokinetics (PK) of inflammatory bowel disease (IBD)-related drugs in pregnant women with IBD. Before evidence-based dosing can be proposed, insight into the PK has to be gained to optimize drug therapy for both mother and fetu...
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| Format: | Article |
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MDPI AG
2022-06-01
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| Series: | Pharmaceutics |
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| Online Access: | https://www.mdpi.com/1999-4923/14/6/1241 |
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| author | Thomas K. Wiersma Marijn C. Visschedijk Nanne K. de Boer Marjolijn N. Lub-de Hooge Jelmer R. Prins Daan J. Touw Paola Mian |
| author_facet | Thomas K. Wiersma Marijn C. Visschedijk Nanne K. de Boer Marjolijn N. Lub-de Hooge Jelmer R. Prins Daan J. Touw Paola Mian |
| author_sort | Thomas K. Wiersma |
| collection | DOAJ |
| description | Due to ethical and practical reasons, a knowledge gap exists on the pharmacokinetics (PK) of inflammatory bowel disease (IBD)-related drugs in pregnant women with IBD. Before evidence-based dosing can be proposed, insight into the PK has to be gained to optimize drug therapy for both mother and fetus. This systematic review aimed to describe the effect of pregnancy and IBD on the PK of drugs used for IBD. One aminosalicylate study, two thiopurine studies and twelve studies with biologicals were included. Most drugs within these groups presented data over multiple moments before, during and after pregnancy, except for mesalazine, ustekinumab and golimumab. The studies for mesalazine, ustekinumab and golimumab did not provide enough data to demonstrate an effect of pregnancy on concentration and PK parameters. Therefore, no evidence-based dosing advice was given. The 6-thioguanine nucleotide levels decreased during pregnancy to 61% compared to pre-pregnancy levels. The potentially toxic metabolite 6-methylmercaptopurine (6-MMP) increased to maximal 209% of the pre-pregnancy levels. Although the PK of the thiopurines changed throughout pregnancy, no evidence-based dosing advice was provided. One study suggested that caution should be exercised when the thiopurine dose is adjusted, due to shunting 6-MMP levels. For the biologicals, infliximab levels increased, adalimumab stayed relatively stable and vedolizumab levels tended to decrease during pregnancy. Although the PK of the biologicals changed throughout pregnancy, no evidence-based dosing advice for biologicals was provided. Other drugs retrieved from the literature search were mesalazine, ustekinumab and golimumab. We conclude that limited studies have been performed on PK parameters during pregnancy for drugs used in IBD. Therefore, more extensive research to determine the values of PK parameters is warranted. After gathering the PK data, evidence-based dosing regimens can be developed. |
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| format | Article |
| id | doaj.art-77f0d6ce4aae4eeab840883089753b6c |
| institution | Directory Open Access Journal |
| issn | 1999-4923 |
| language | English |
| last_indexed | 2024-03-09T22:45:33Z |
| publishDate | 2022-06-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceutics |
| spelling | doaj.art-77f0d6ce4aae4eeab840883089753b6c2023-11-23T18:30:32ZengMDPI AGPharmaceutics1999-49232022-06-01146124110.3390/pharmaceutics14061241The Effect of Pregnancy and Inflammatory Bowel Disease on the Pharmacokinetics of Drugs Related to Inflammatory Bowel Disease—A Systematic Literature ReviewThomas K. Wiersma0Marijn C. Visschedijk1Nanne K. de Boer2Marjolijn N. Lub-de Hooge3Jelmer R. Prins4Daan J. Touw5Paola Mian6Department of Clinical Pharmacy and Pharmacology, University Medical Center Groningen, 9713 GZ Groningen, The NetherlandsDepartment of Gastroenterology and Hepatology, University Medical Center Groningen, 9713 GZ Groningen, The NetherlandsDepartment of Gastroenterology and Hepatology, AGEM Research Institute, Amsterdam University Medical Centre, Vrije Universiteit Amsterdam, 1081 HV Amsterdam, The NetherlandsDepartment of Clinical Pharmacy and Pharmacology, University Medical Center Groningen, 9713 GZ Groningen, The NetherlandsDepartment of Obstetrics and Gynecology, University Medical Center Groningen, 9713 GZ Groningen, The NetherlandsDepartment of Clinical Pharmacy and Pharmacology, University Medical Center Groningen, 9713 GZ Groningen, The NetherlandsDepartment of Clinical Pharmacy and Pharmacology, University Medical Center Groningen, 9713 GZ Groningen, The NetherlandsDue to ethical and practical reasons, a knowledge gap exists on the pharmacokinetics (PK) of inflammatory bowel disease (IBD)-related drugs in pregnant women with IBD. Before evidence-based dosing can be proposed, insight into the PK has to be gained to optimize drug therapy for both mother and fetus. This systematic review aimed to describe the effect of pregnancy and IBD on the PK of drugs used for IBD. One aminosalicylate study, two thiopurine studies and twelve studies with biologicals were included. Most drugs within these groups presented data over multiple moments before, during and after pregnancy, except for mesalazine, ustekinumab and golimumab. The studies for mesalazine, ustekinumab and golimumab did not provide enough data to demonstrate an effect of pregnancy on concentration and PK parameters. Therefore, no evidence-based dosing advice was given. The 6-thioguanine nucleotide levels decreased during pregnancy to 61% compared to pre-pregnancy levels. The potentially toxic metabolite 6-methylmercaptopurine (6-MMP) increased to maximal 209% of the pre-pregnancy levels. Although the PK of the thiopurines changed throughout pregnancy, no evidence-based dosing advice was provided. One study suggested that caution should be exercised when the thiopurine dose is adjusted, due to shunting 6-MMP levels. For the biologicals, infliximab levels increased, adalimumab stayed relatively stable and vedolizumab levels tended to decrease during pregnancy. Although the PK of the biologicals changed throughout pregnancy, no evidence-based dosing advice for biologicals was provided. Other drugs retrieved from the literature search were mesalazine, ustekinumab and golimumab. We conclude that limited studies have been performed on PK parameters during pregnancy for drugs used in IBD. Therefore, more extensive research to determine the values of PK parameters is warranted. After gathering the PK data, evidence-based dosing regimens can be developed.https://www.mdpi.com/1999-4923/14/6/1241inflammatory bowel diseasepregnancypharmacokinetics |
| spellingShingle | Thomas K. Wiersma Marijn C. Visschedijk Nanne K. de Boer Marjolijn N. Lub-de Hooge Jelmer R. Prins Daan J. Touw Paola Mian The Effect of Pregnancy and Inflammatory Bowel Disease on the Pharmacokinetics of Drugs Related to Inflammatory Bowel Disease—A Systematic Literature Review Pharmaceutics inflammatory bowel disease pregnancy pharmacokinetics |
| title | The Effect of Pregnancy and Inflammatory Bowel Disease on the Pharmacokinetics of Drugs Related to Inflammatory Bowel Disease—A Systematic Literature Review |
| title_full | The Effect of Pregnancy and Inflammatory Bowel Disease on the Pharmacokinetics of Drugs Related to Inflammatory Bowel Disease—A Systematic Literature Review |
| title_fullStr | The Effect of Pregnancy and Inflammatory Bowel Disease on the Pharmacokinetics of Drugs Related to Inflammatory Bowel Disease—A Systematic Literature Review |
| title_full_unstemmed | The Effect of Pregnancy and Inflammatory Bowel Disease on the Pharmacokinetics of Drugs Related to Inflammatory Bowel Disease—A Systematic Literature Review |
| title_short | The Effect of Pregnancy and Inflammatory Bowel Disease on the Pharmacokinetics of Drugs Related to Inflammatory Bowel Disease—A Systematic Literature Review |
| title_sort | effect of pregnancy and inflammatory bowel disease on the pharmacokinetics of drugs related to inflammatory bowel disease a systematic literature review |
| topic | inflammatory bowel disease pregnancy pharmacokinetics |
| url | https://www.mdpi.com/1999-4923/14/6/1241 |
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