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 Experiment | |
|---|---|
| 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 Experiment | |
|---|---|
| Animal models | CD1 mice |
| Formulation | PBS |
| Dosages | 1 ml/100 g b.wt |
| Administration | i.p. |
| CAS Number | 331731-18-1 |
| Storage | Store at -20°C or -70°C. Avoid multiple freeze-thaws. |
| Species | Mouse | Rat | Rabbit | Guinea pig | Hamster | Dog |
| Weight (kg) | 0.02 | 0.15 | 1.8 | 0.4 | 0.08 | 10 |
| Body Surface Area (m2) | 0.007 | 0.025 | 0.15 | 0.05 | 0.02 | 0.5 |
| Km factor | 3 | 6 | 12 | 8 | 5 | 20 |
| 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.
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