The effects of pregnancy on the pharmacokinetics of infliximab and adalimumab in inflammatory bowel disease
| Autor: | Divine Tanyingoh, Cynthia H. Seow, Gurmeet K. Bindra, M J Stewart, Subrata Ghosh, Remo Panaccione, N. Vande Casteele, Paul L. Beck, Gilaad G. Kaplan, E. Ehteshami Afshar, Yvette Leung |
|---|---|
| Rok vydání: | 2017 |
| Předmět: |
Adult
musculoskeletal diseases medicine.medical_specialty Adolescent Placenta Antibodies Monoclonal Humanized Inflammatory bowel disease Gastroenterology Young Adult 03 medical and health sciences 0302 clinical medicine Crohn Disease Pharmacokinetics Pregnancy Internal medicine medicine Adalimumab Humans Placental Circulation Pharmacology (medical) Dosing skin and connective tissue diseases Maternal-Fetal Exchange Hepatology medicine.diagnostic_test Tumor Necrosis Factor-alpha business.industry Inflammatory Bowel Diseases medicine.disease Ulcerative colitis Infliximab Surgery Therapeutic drug monitoring 030220 oncology & carcinogenesis Colitis Ulcerative Female 030211 gastroenterology & hepatology Drug Monitoring business medicine.drug |
| Zdroj: | Alimentary Pharmacology & Therapeutics. 45:1329-1338 |
| ISSN: | 0269-2813 |
| Popis: | Background Transplacental transfer of infliximab and adalimumab results in detectable drug levels in the cord blood and infant. Aim To determine if pregnancy influenced the pharmacokinetics of anti-TNF agents in women with inflammatory bowel disease. Methods Twenty-five women from the University of Calgary inflammatory bowel disease(IBD) pregnancy clinic on maintenance infliximab or adalimumab were recruited prospectively with serum bio-banking performed each trimester. Infliximab trough and adalimumab steady-state levels were the outcomes of interest and were analysed using the ANSER infliximab and adalimumab assays. Multivariate linear mixed-effects models were constructed to assess infliximab and adalimumab drug levels during pregnancy adjusting for the clinical covariates of albumin, BMI and CRP. Results Fifteen women (eight Crohn's disease, seven ulcerative colitis) received infliximab and 10 women with 11 pregnancies were treated with adalimumab. Median age was 29.6 years (IQR: 27.6–31.2 years). Median disease duration was 9.2 years (IQR: 3.16–15.0 years). Median trough infliximab concentrations were 8.50 μg/mL (IQR: 7.23–10.07 μg/mL), 10.31 μg/mL (IQR: 7.66–15.63 μg/mL) and 21.02 μg/mL (IQR: 16.01–26.70 μg/mL) at trimesters 1, 2 and 3 respectively. Significant changes in albumin and BMI (P 0.05) were documented throughout pregnancy. After adjusting for albumin, BMI and CRP, infliximab trough levels increased during pregnancy, by 4.2 μg/mL per trimester (P = 0.02), while adalimumab drug levels remained stable (P > 0.05). Conclusions Infliximab levels rise during pregnancy, whereas adalimumab levels remain stable after accounting for changes in albumin, BMI and CRP. Therapeutic drug monitoring in the second trimester may be useful in guiding dosing in the third trimester. |
| Databáze: | OpenAIRE |
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