Bioavailability and Biological Efficacy of a New Oral Formulation of Salmon Calcitonin in Healthy Volunteers

Authors

  • Thierry Buclin,

    Corresponding author
    1. Division of Clinical Pharmacology, University Hospital of Lausanne (CHUV), Lausanne, Switzerland
    • Division of Clinical Pharmacology, University Hospital of Lausanne (CHUV), Hôpital Beaumont 633, CH-1011 Lausanne, Switzerland
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    • Dr. Thierry Buclin and Dr. Monica Cosma Rochat contributed equally in this work.

  • Monica Cosma Rochat,

    1. Division of Clinical Pharmacology, University Hospital of Lausanne (CHUV), Lausanne, Switzerland
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    • Dr. Thierry Buclin and Dr. Monica Cosma Rochat contributed equally in this work.

  • Peter Burckhardt,

    1. Department of Medicine, Service A, University Hospital of Lausanne (CHUV), Lausanne, Switzerland
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  • Moïse Azria,

    1. Novartis Pharma International, Basle, Switzerland
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  • Martine Attinger

    1. Novartis Pharma International, Basle, Switzerland
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    • Dr. Attinger has financial interests in the forms of corporate appointments and stock options with Novartis. Dr. Azria has financial interests in the form of corporate appointments and stock options with Novartis and has an agreement with Novartis and Emisphere. Dr. Buclin's institution (University Hospital of Lausanne) received funds for the conduct of the study. Dr. Burckhardt has financial interests in the form of stock ownership and serves as a consultant. He also is a member of the Board of Directors of Novartis. Dr. Cosma Rochat's institution (University Hospital of Lausanne) received funds for the conduct of the study.


  • Presented at the 23rd annual meeting of the American Society for Bone and Mineral Research, October 16, 2001, Phoenix, Arizona, USA.

Abstract

Salmon calcitonin (SCT) is a well-tolerated peptide drug with a wide therapeutic margin and is administered parenterally for long-term treatments of bone diseases. Its clinical usefulness would be enhanced by the development of an orally active formulation. In this randomized crossover double-blinded phase I trial, controlled by both a placebo and a parenteral verum, we have tested a new oral formulation of SCT associated with a caprylic acid derivative as carrier. Eight healthy volunteers received single doses of 400, 800, and 1200 μg of SCT orally, a placebo, and a 10-μg (50 IU) SCT intravenous infusion. SCT was reliably absorbed from the oral formulation, with an absolute bioavailability of 0.5–1.4%, depending on the dose. It induced a marked, dose-dependent drop in blood and urine C-terminal telopeptide of type I collagen (CTX), a sensitive and specific bone resorption marker, with the effects of 1200 μg exceeding those of 10 μg intravenously. It also decreased blood calcium and phosphate, and increased the circulating levels of parathyroid hormone (PTH) and, transiently, the urinary excretion of calcium. It was well-tolerated, with some subjects presenting mild and transient nausea, abdominal cramps, diarrheic stools, and headaches. This study shows that oral delivery of SCT is feasible with reproducible absorption and systemic biological efficacy. Such an oral formulation could facilitate the use of SCT in the treatment of osteoporosis and other bone diseases.

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