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| Primary information |
|---|
| ID | 10826 |
| Therapeutic ID | Th1192 |
| Protein Name | Ustekinumab |
| Sequence | >Th1192_Ustekinumab
EVQLVQSGAEVKKPGESLKISCKGSGYSFTTYWLGWVRQMPGKGLDWIGIMSPVDSDIRYSPSFQGQVTMSVDKSITTAYLQWNSLKASDTAMYYCARRRPGQGYFDFWGQGTLVTVSSSSTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSCDKTH
|
| Molecular Weight | 148600 |
| Chemical Formula | NA |
| Isoelectric Point | NA |
| Hydrophobicity | NA |
| Melting point | NA |
| Half-life | Following administration of a single subcutaneous dose of 45 mg or 90 mg in patients with psoriasis, the median half-life was 19.8 days and 21.2, respectively. |
| Description | CNTO 1275 is the experimental name for the human immunosuppressive drug ustekinumab developed by the biotechnology company Centocor. It is a laboratory manufactured, monoclonal antibody directed against interleukins IL-12 and IL-23. |
| Indication/Disease | For treatment in psoriasis and psoriatic disorders. |
| Pharmacodynamics | NA |
| Mechanism of Action | Similar to the immunosuppressive function of Etanercept (Enbrel), CNTO 1275 is designed to interfere with the triggering of the body's inflamatory response through the suppression of certain cytokines. Specifically, CNTO 1275 blocks interleukin IL-12 and IL-23 (via the p40 subunit of IL-12 and IL-23) which help activate certain T-cells. |
| Toxicity | Signs of dose-limiting toxicity were not observed with intravenous administration of single doses up to 6 mg/kg in clinical trials. Information on overdose of ustekinumab is limited: in the event of overdose, patients should be monitored for any signs and symptoms of drug-related adverse events and appropriate symptomatic treatment should be initiated.[L9383,L9386] |
| Metabolism | The metabolic pathway of ustekinumab has not been fully characterized; it is expected to undergo nonspecific protein degradation via catabolic pathways in the same manner as endogenous IgG.[L9383,L9386] |
| Absorption | The median Tmax following a single subcutaneous dose administration of 45mg and 90mg in adults with psoriasis was 13.5 days and 7 days, respectively. The median Cmax in the same group of patients was 2.4 µg/mL and 5.3 µg/mL at doses of 45mg and 90mg, respectively. The median AUC was 84.9 µg·day/mL and 226.9 µg·day/mL, respectively.[L9491] Following an intravenous induction dose administration, the mean ± SD Cmax was 125.2 ± 33.6 mcg/mL in patients with Crohn’s disease and 129.1 ± 27.6 mcg/mL in patients with ulcerative colitis.[L9386] The systemic exposure of ustekinumab (Cmax and AUC) increases in a linear or dose-proportional manner following a single subcutaneous administration at doses ranging from approximately 24 mg to 240 mg in patients with psoriasis. The estimated absolute bioavailability (F) of ustekinumab following a single subcutaneous dose administration in patients with psoriasis is 57.2%.[L9491] |
| The total volume of distribution at steady-state was 4.62 L in patients with Crohn’s disease and 4.4 L in patients with ulcerative colitis.[L9386] The median apparent volume of distribution during the terminal phase (Vz/F) ranged from 76 to 161 mL/kg in patients with psoriasis receiving a single subcutaneous dose.[L9491] |
| Clearance | The median apparent clearance (CL/F) following a single subcutaneous administration to patients with psoriasis ranged from 2.7 to 5.3 mL/day/kg.[L9491] In patients with Crohn’s disease, the clearance was 0.19 L/day in patients with Crohn’s disease or ulcerative colitis.[L9383,L9386] |
| Categories | Deramtologic agent, Immunosuppressive agent, antineoplastic agent |
| Patents Number | NA |
| Date of Issue | NA |
| Date of Expiry | NA |
| Drug Interaction | Belimumab, Denosumab, Infliximab, Leflunomide, Natalizumab, Pimecrolimus, Roflumilast, Sipuleucel-T, Tacrolimus, Tofacitinib, Trastuzumab |
| Target | Interleukin-12 subunit beta,Interleukin-23 |
| Brand Name | Stelara |
| Company | Janssen Biotech, Inc. |
| Brand Description | Janssen Biotech, Inc. |
| Prescribed For | Psoriasis (Ps) and Psoriatic Arthritis (PsA) |
| Chemical Name | NA |
| Formulation | Each 45 mg ustekinumab prefilled syringe also contains: L-histidine and L-histidine monohydrochloride monohydrate (0.5 mg), Polysorbate 80 (0.02 mg), and sucrose (38 mg) to fill to a final volume of 0.5 mL. |
| Physical Appearance | solution fro injection |
| Route of Administration | Subcutaneous |
| Recommended Dosage | In case of psoriasis, for patients weighing ≤ 100 kg (220 lbs), the recommended dose is 45 mg initially and 4 weeks later, followed by 45 mg every 12 weeks. In case of Psoriatic Arthritis ecommended dose is 45 mg initially and 4 weeks later, followed by 45 mg every 12 weeks. |
| Contraindication | NA |
| Side Effects | Adverse reactions that occurred at rates less than 1% in the controlled period of Ps STUDIES 1 and 2 through week 12 included: cellulitis, herpes zoster, diverticulitis and certain injection site reaction |
| Useful Link 1 | Link |
| Useful Link 2 | NA |
| Remarks | NA |