Clinical Pharmacokinetic and Pharmacodynamic Considerations in the Treatment of Ulcerative Colitis

Berends, Sophie E.; Strik, Anne S.; Löwenberg, Mark; D’Haens, Geert R.; Mathôt, Ron A. A.

doi:10.1007/s40262-018-0676-z

Cited by 99 publications

(71 citation statements)

References 222 publications

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“…As an IgG monoclonal antibody, pharmacokinetic properties of vedolizumab should be expected to be similar to the anti-TNF agents. 17 Vedolizumab exhibits a slower, linear elimination at levels above 10 µg/mL, but rapid, saturable, non-linear elimination at lower concentrations. 23 Clearance also appears increased with higher body weight and low albumin.…”

Section: Discussionmentioning

confidence: 97%

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Infliximab, adalimumab and vedolizumab concentrations across pregnancy and vedolizumab concentrations in infants following intrauterine exposure

Flanagan¹,

Gibson

Wright³

et al. 2020

Aliment Pharmacol Ther

101

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Background: The impact of pregnancy on levels of biologic agents in patients with IBD is undefined and time to elimination in vedolizumab-exposed infants is unknown. Aims: To determine the effect of pregnancy on infliximab, adalimumab and vedolizumab levels and to study infant vedolizumab clearance Methods: In a prospective observational study, maternal drug levels were measured pre-conception, in each trimester, at delivery and postpartum. The association between drug levels and gestation in weeks was assessed using generalised estimating equation modelling. Infant vedolizumab levels were performed at birth (cord blood), 6 weeks and 3 months or until undetectable. Results: We included 50 IBD patients (23 on infliximab, 15 on adalimumab and 12 on vedolizumab) with at least two intrapartum observations, plus 5 patients on vedolizumab with only mother and baby samples at delivery. Modelling showed no change in adalimumab levels, an increase in infliximab levels of 0.16 (95% CI 0.08-0.24) µg/L/week (P < 0.001) and a decrease of 0.18 (95% CI: −0.33 to −0.02) µg/L/week (P = 0.03) for vedolizumab. In 17 mother-baby pairs, median infant vedolizumab levels at birth were lower than maternal levels (P < 0.05) with an infant:maternal ratio of 0.7 (IQR 0.5-0.9). Vedolizumab was undetectable between 15 and 16 weeks of age in all 12 infants completing follow-up testing. Conclusions: During pregnancy, adalimumab levels remain stable, while infliximab levels increase and vedolizumab levels decrease. However, the increments were small suggesting that intrapartum therapeutic drug monitoring and dose adjustment are not indicated. Unlike infliximab and adalimumab, infant vedolizumab levels are lower in cord blood than in mothers and appear to clear rapidly.

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Section: Discussionmentioning

confidence: 97%

“…bodies, the type of anti-TNF drug 7 and more severe disease activity. 16,17 The marked physiological changes that occur in association with pregnancy might be anticipated to change the clearance of these drugs. The clearance of many drugs is known to be increased during pregnancy, 18 therefore, lower drug levels may be expected.…”

Section: Discussionmentioning

confidence: 99%

Infliximab, adalimumab and vedolizumab concentrations across pregnancy and vedolizumab concentrations in infants following intrauterine exposure

Flanagan¹,

Gibson

Wright³

et al. 2020

Aliment Pharmacol Ther

101

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“… 3 , 4 At present, the main pharmacological treatment options for IBD patients include aminosalicylic acid, glucocorticoids, antibiotics, immunosuppressants, and biological agents. 5 These drugs exert therapeutic effects in patients with IBD through regulating inflammation in the microenvironment, but long-term use of these drugs may cause side effects and increase risk of developing other diseases. 6 As such, new treatments for IBD are needed.…”

Section: Introductionmentioning

confidence: 99%

Selenium-Containing Amino Acids Protect Dextran Sulfate Sodium-Induced Colitis via Ameliorating Oxidative Stress and Intestinal Inflammation

Shi¹,

Yue²,

Shi³

et al. 2021

JIR

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“…Ulcerative colitis (UC) is an inflammatory bowel disease (IBD) caused by a combination of environmental and genetic factors and is characterized by inflammation, homeostasis disruption, and epithelial barrier damage in the intestinal tract [1, 2]. UC affects millions of people worldwide, and its morbidity increases yearly.…”

Section: Introductionmentioning

confidence: 99%

Dihydroartemisinin Protects against Dextran Sulfate Sodium-Induced Colitis in Mice through Inhibiting the PI3K/AKT and NF-κB Signaling Pathways

Sun

Zhou

et al. 2019

BioMed Research International

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Ulcerative colitis is a common inflammatory bowel disease, and the activation of thePI3K/AKT and NF-κB signaling pathways plays a pivotal role in its pathogenesis. Dihydroartemisinin (DHA) is a widely used antimalarial drug and has shown anticancer effect partially through inhibiting the activation of PI3K/AKT and NF-κB. This study aimed to investigate the effect of dihydroartemisinin on ulcerative colitis and its mechanism. Adult male C57 mice were subjected to 3.0% dextran sulfate sodium (DSS) for seven days; simultaneously, dihydroartemisinin or control saline was administered by oral gavage once a day. In vitro, the intestinal epithelial cell-6 was treated with LPS for 24 hours with or without dihydroartemisinin combined with PI3K/Akt activator 740 Y-P or NF-κB activator phorbol myristate acetate. Western blotting was used to test the activation of PI3K/AKT and NF-κB. Dihydroartemisinin significantly ameliorated body weight loss, shortened colon length, and increased DAI in DSS-induced colitis. Meanwhile, histological damage was improved and was accompanied by decreased expression and secretion of proinflammatory cytokines. Moreover, DSS-induced elevation of phosphorylation of PI3K, AKT, IKKα, IκBα, and NF-κB (p65) was remarkably blunted by dihydroartemisinin both in vivo and in vitro, indicating an inhibitive property on the PI3K/AKT and NF-κB signaling pathways. Furthermore, administration of 740 Y-P or PMA significantly blocked protective activity of dihydroartemisinin against colitis in vitro. In conclusion, dihydroartemisinin can attenuate DSS-induced colitis, and its anticolitis effect might be mediated via the PI3K/AKT and NF-κB signaling pathways. DHA might serve as a promising drug for patients with ulcerative colitis.

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Clinical Pharmacokinetic and Pharmacodynamic Considerations in the Treatment of Ulcerative Colitis

Abstract: Ulcerative colitis (UC) is an inflammatory bowel disease (IBD) of unknown etiology, probably caused by a combination of genetic and environmental factors. The treatment of patients with active UC depends on the severity, localization and history of IBD medication.

Cited by 99 publications

References 222 publications

Infliximab, adalimumab and vedolizumab concentrations across pregnancy and vedolizumab concentrations in infants following intrauterine exposure

Infliximab, adalimumab and vedolizumab concentrations across pregnancy and vedolizumab concentrations in infants following intrauterine exposure

Selenium-Containing Amino Acids Protect Dextran Sulfate Sodium-Induced Colitis via Ameliorating Oxidative Stress and Intestinal Inflammation

Dihydroartemisinin Protects against Dextran Sulfate Sodium-Induced Colitis in Mice through Inhibiting the PI3K/AKT and NF-κB Signaling Pathways

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