In vitro: Adalimumab blocks the interaction of TNF with the p55 and p75 cell surface TNF receptors, thereby neutralising the activity of this cytokine. Through its anti-TNF actions, adalimumab reduces concentrations of matrix metalloproteases (MMP-1 and -3) and other markers of cartilage and synovium turnover, reduces of matrix metalloproteases (MMP-1 and -3) and other markers of cartilage and synovium turnover, and reduces concentrations of acute phase reactants of inflammation (C-reactive protein [CRP] and erythrocyte sedimentation rate [ESR]) and serum cytokines (IL-1β mRNA, IL-1 receptor antagonist, IL-6).
In vivo: Adalimumab is safe and well tolerated. In healthy adults, the average absolute bioavailability of adalimumab 40 mg administered subcutaneously (s.c.) is 64%. Concentrations in the synovial fluid are 31-96% of those of the serum. Maximum plasma concentrations occur at 131 (± 56) h, and the mean half-life is ∼ 2 weeks (range, 10-20 days). Adalimumab treatment attenuates the Ovalbumin(OVA)-induced increase in serum IgE, TH2 and TH1 derived inflammatory cytokines (IL-4 and IFN-γ, respectively) in bronchoalveolar lavage (BAL) fluid, suppresses recruitment of inflammatory cells in BAL fluid and lung, and inhibits BAL fluid neutrophilia. It also ameliorates goblet cell metaplasia and bronchial fibrosis.
|Cell lines||Caco-2 BBE cells|
|Preparation method||T-84 and Caco-2 cells grown on transwell inserts were primed with IFN-γ (2.5 and 5 ng/ml, respectively) for 24 h followed by treatment with TNF-α (5 ng/ml), adalimumab (10 μg/ ml), or both.|
|Concentrations||10 μg/ ml|
|Incubation time||24 h|
|Animal models||CD1 mice|
|Dosages||1 ml/100 g b.wt|
|Storage||Store at -20°C or -70°C. Avoid multiple freeze-thaws.|
|Body Surface Area (m2)||0.007||0.025||0.15||0.05||0.02||0.5|
|Animal A (mg/kg) = Animal B (mg/kg) multiplied by||Animal B Km|
|Animal A Km|
For example, to modify the dose of Compound A used for a mouse (20 mg/kg) to a dose based on the BSA for a rat, multiply 20 mg/kg by the Km factor for a mouse and then divide by the Km factor for a rat. This calculation results in a rat equivalent dose for Compound A of 10 mg/kg.
 Fischer A, et al. Am J Physiol Gastrointest Liver Physiol. Adalimumab prevents barrier dysfunction and antagonizes distinct effects of TNF-α on tight junction proteins and signaling pathways in intestinal epithelial cells.
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