Albubnp, a Recombinant B-type Natriuretic Peptide and Human Serum Albumin Fusion Hormone, as a Long-Term Therapy of Congestive Heart Failure View Full Text


Ontology type: schema:ScholarlyArticle     


Article Info

DATE

2004-11

AUTHORS

Wei Wang, Ying Ou, Yanggu Shi

ABSTRACT

Purpose. B-type natriuretic peptide (BNP) has been in clinical use for the treatment of decompensated congestive heart failure. However, BNP has a very short half-life in circulation, which limits its application to acute CHF and requires continuous i.v. infusion. To provide superior pharmacological benefits of BNP to other stages of chronic congestive heart failure and to eliminate problems associated with drug delivery via continuous i.v. infusion, we have designed and evaluated AlbuBNP, a long-acting form of BNP by recombinant fusion to human serum albumin for use in chronic congestive heart failure, post-acute follow-up, and postmyocardial infarction.Method. Human BNP (1-32) was seamlessly fused to mature human serum albumin at N-terminus to create AlbuBNP. The bioactivities of AlbuBNP were evaluated by natriuretic peptide receptor-A mediated cGMP activation assay, hemodynamic responses, and plasma cGMP elevation. The pharmacokinetic properties were determined after single i.v. or s.c. bolus injection in C57/BL6 mice.Results. AlbuBNP had approxiamtely the same maximal bioactivity as BNP to activate cGMP in the in vitro NPRA/cGMP assay. The EC50s were 28.4 ± 1.2 and 0.46 ± 1.1 nM for AlbuBNP and BNP, respectively. In spontaneously hypertensive rats, AlbuBNP lowered both systolic and diastolic blood pressure, having sustainable mean arterial pressure reduction for more than 2 days. Six nmol/kg AlbuBNP i.v. bolus in mice increased plasma cGMP level 5.6-fold over the baseline. The elimination half-life in mice was dramatically increased from 3 min for BNP to 12-19 h for AlbuBNP.Conclusions. AlbuBNP is bioactive and has desired pharmacokinetic properties for long-term use. It has the potential to be further developed as a new therapeutic option for chronic, acute, and post-acute CHF to alleviate symptoms, improve clinical status, and slow the disease progression by sustained drug exposure via infrequent simple subcutaneous injections. More... »

PAGES

2105-2111

References to SciGraph publications

  • 2003-10. B-Type Natriuretic Peptide: Spectrum of Application. Nesiritide (Recombinant BNP) for Heart Failure in HEART FAILURE REVIEWS
  • 2003-03. Nesiritide in CARDIOVASCULAR TOXICOLOGY
  • 2003-11-18. Effect of albumin fusion on the biodistribution of interleukin-2 in CANCER IMMUNOLOGY, IMMUNOTHERAPY
  • 2003-01. Nesiritide in DRUGS
  • Journal

    TITLE

    Pharmaceutical Research

    ISSUE

    11

    VOLUME

    21

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  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1023/b:pham.0000048203.30568.81

    DOI

    http://dx.doi.org/10.1023/b:pham.0000048203.30568.81

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1004340827

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/15587934


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