Dr. Thierry Buclin and Dr. Monica Cosma Rochat contributed equally in this work.
Bioavailability and Biological Efficacy of a New Oral Formulation of Salmon Calcitonin in Healthy Volunteers†
Article first published online: 1 AUG 2002
Copyright © 2002 ASBMR
Journal of Bone and Mineral Research
Volume 17, Issue 8, pages 1478–1485, August 2002
How to Cite
Buclin, T., Rochat, M. C., Burckhardt, P., Azria, M. and Attinger, M. (2002), Bioavailability and Biological Efficacy of a New Oral Formulation of Salmon Calcitonin in Healthy Volunteers. J Bone Miner Res, 17: 1478–1485. doi: 10.1359/jbmr.2002.17.8.1478
Presented at the 23rd annual meeting of the American Society for Bone and Mineral Research, October 16, 2001, Phoenix, Arizona, USA.
- Issue published online: 2 DEC 2009
- Article first published online: 1 AUG 2002
- Manuscript Accepted: 19 MAR 2002
- Manuscript Revised: 13 FEB 2002
- Manuscript Received: 20 NOV 2001
- oral administration;
- intestinal absorption;
- bone resorption markers;
- healthy humans
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.