Peringatan Keamanan

Supportive treatment is recommended in case of overdose. Use of Inductos in patients undergoing cervical spine surgery in amounts lower than or similar to those for lumbar interbody fusion has been associated with reports of localised oedema severe enough to result in airway compromise L1391.

There is no evidence of significant hazards on humans based on non-clinical data of acute and repeated exposure toxicity and genotoxicity studies L1391. In reproductive toxicity studies in rats, intravenous administration of dibotermin alfa was associated with increased fetal weight and increased fetal ossification. The clinical relevance of this effect is unknown L1391. In human tumour cell lines in vitro, dibotermin alfa did not display any potential for promotion of tumour growth or metastasis L1391. Studies investigating the carcinogenicity of dibotermin alfa have not been conducted.

Dibotermin alfa

DB11639

biotech approved investigational

Deskripsi

Dibotermin alfa is a recombinant human bone morphogenetic protein-2 (rhBMP-2) derived from a recombinant Chinese Hamster Ovary (CHO) cell line FDA Label. It is implanted in patients undergoing bone surgeries or those with fractures. BMPs are subfamily of the transforming growth factor-? (TGF-?) superfamily that have different actions on the bone matrix A31946. BMP-2 is a potent osteoinductive protein that plays a critical role in the differentiation of osteoprogenitor cells into osteoblasts, thus promoting bone and cartilage formation A31952. Through enhancing osteogenesis at the site of implantation, dibotermin alfa accelerates the healing of open tibial shaft fractures and reduces the need for secondary intervention A31945. In a prospective clinical study of patients with an open tibial fracture, administration of dibotermin alfa resulted in faster fracture- or wound-healing, significantly fewer secondary invasive interventions, and reduced infection rate post-operation A31945. Dibotermin alfa was approved by the EMA in 2002 as Inductos for implantation matrix. In 2004, it was approved by the FDA and is marketed as Infuse. In Infuse, rhBMP is a disulfide-linked dimeric protein molecule with two major subunit species of 114 and 131 amino acids. Each subunit is glycosylated with high-mannose-type glycans FDA Label.

Struktur Molekul 2D

Struktur tidak tersedia

Peta Jejaring Molekuler
Legenda: ObatTargetGenEnzim(Panah → menunjukkan arah efek / relasi)TransporterCarrier

Profil Farmakokinetik

Waktu Paruh (Half-Life) When injected intravenously, the terminal half-life of dibotermin alfa was 16 minutes in rats and 6.7 minutes in cynomolgus monkeys [L1391].
Volume Distribusi -
Klirens (Clearance) At the site of implantation, dibotermin alfa is expected to be slowly released from the matrix and rapidly cleared when taken up into the systemic circulation [L1391].

Absorpsi

Dibotermin alfa is active at the site of implantation with no detection in the serum. In rat studies with radiolabelled dibotermin alfa, the mean residence time at the site of implantation was 4-8 days L1391. Peak levels of circulating dibotermin alfa (0.1% of the implanted dose) were observed within 6 hours following implantation L1391.

Metabolisme

Data metabolisme tidak tersedia.

Rute Eliminasi

As recombinant human bone morphogenetic protein-2 (BMP-2), dibotermin alfa is expected to undergo nonspecific protein degradation pathway shared by endogenous BMP-2.

Interaksi Obat

0 Data
Tidak ada data.

Target Protein

Bone morphogenetic protein receptor type-2 BMPR2
Bone morphogenetic protein receptor type-1A BMPR1A

Referensi & Sumber

Artikel (PubMed)
  • PMID: 12473698
    Govender S, Csimma C, Genant HK, Valentin-Opran A, Amit Y, Arbel R, Aro H, Atar D, Bishay M, Borner MG, Chiron P, Choong P, Cinats J, Courtenay B, Feibel R, Geulette B, Gravel C, Haas N, Raschke M, Hammacher E, van der Velde D, Hardy P, Holt M, Josten C, Ketterl RL, Lindeque B, Lob G, Mathevon H, McCoy G, Marsh D, Miller R, Munting E, Oevre S, Nordsletten L, Patel A, Pohl A, Rennie W, Reynders P, Rommens PM, Rondia J, Rossouw WC, Daneel PJ, Ruff S, Ruter A, Santavirta S, Schildhauer TA, Gekle C, Schnettler R, Segal D, Seiler H, Snowdowne RB, Stapert J, Taglang G, Verdonk R, Vogels L, Weckbach A, Wentzensen A, Wisniewski T: Recombinant human bone morphogenetic protein-2 for treatment of open tibial fractures: a prospective, controlled, randomized study of four hundred and fifty patients. J Bone Joint Surg Am. 2002 Dec;84-A(12):2123-34.
  • PMID: 21698428
    Lissenberg-Thunnissen SN, de Gorter DJ, Sier CF, Schipper IB: Use and efficacy of bone morphogenetic proteins in fracture healing. Int Orthop. 2011 Sep;35(9):1271-80. doi: 10.1007/s00264-011-1301-z. Epub 2011 Jun 23.
  • PMID: 9879521
    Takiguchi T, Kobayashi M, Suzuki R, Yamaguchi A, Isatsu K, Nishihara T, Nagumo M, Hasegawa K: Recombinant human bone morphogenetic protein-2 stimulates osteoblast differentiation and suppresses matrix metalloproteinase-1 production in human bone cells isolated from mandibulae. J Periodontal Res. 1998 Nov;33(8):476-85.
  • PMID: 19707367
    Ghodadra N, Singh K: Recombinant human bone morphogenetic protein-2 in the treatment of bone fractures. Biologics. 2008 Sep;2(3):345-54.

Contoh Produk & Brand

Produk: 2 • International brands: 0
Produk
  • Inductos
    - • 1.5 mg/ml • - • EU • Approved
  • Inductos
    - • 1.5 mg/ml • - • EU • Approved

Sekuens Gen/Protein (FASTA)

Sekuens dimuat saat dibutuhkan agar halaman tetap ringan.
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