Influence of food intake on the bioavailability and efficacy of oral calcitonin

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT • No orally bioavailable peptides are currently approved by the US Food and Drug Administration or the European Medicines Agency. • Attempts have been made to develop an oral formulation of salmon calcitonin (sCT). • However, the effect of food intake on the bioavailability and efficacy of oral peptide formulations has not been systematically investigated. WHAT THIS STUDY ADDS • We provide evidence that oral doses of sCT may be optimally received in the fasting state or prior to meal intake. • Fasting or preprandial dosing led to improved bioavailability and effect on pharmacodynamic biomarkers of efficacy. • The results may aid other researchers involved in the formulation of oral peptides. AIMS To investigate the influence of food intake on the bioavailability and pharmacodynamic effects of salmon calcitonin (sCT). METHODS A single-blind, randomized, partly placebo-controlled study was conducted in 36 healthy postmenopausal female volunteers aged 62–74 years. The influence of food intake on oral dosing with 0.8 mg of sCT at 22.00 h was evaluated for a (i) predose meal at 18.00 h, (ii) predose meal at 20.00 h, (iii) predose meal at 21.00 h, (iv) postdose meal at 22.10 h, (v) no meal, and (vi) meal at 20.00 h and placebo at 22.00 h. Study biomarkers were plasma sCT levels and changes in the bone resorption marker CTX-I (C-terminal telopeptide of collagen type I). RESULTS The predose meal at 18.00 and 21.00 h significantly decreased relative oral bioavailability of sCT to 26% [95% confidence interval (CI) 0.09, 0.73 and 0.09, 0.75, P= 0.009 and P= 0.01]. The meal consumed 10 min after dosing decreased the oral bioavailability of sCT to 59% (95% CI 0.21, 1.68), although nonsignificant (P= 0.48). This decreased bioavailability led to lower relative suppression of serum CTX-I, with an AUC of the 4-h efficacy response of −91%–×–hours for those receiving a meal at 18.00 h, compared with −238%–×–hours for fasting subjects. The Dunnett-adjusted difference between these two treatment sequences was 147%–×–hours (95% CI 68, 225) (P= 0.0003). The AUC was comparable among fasting subjects and those consuming a meal 10 min after dosing. CONCLUSIONS Postprandial dosing may limit the bioavailability of orally administered sCT. Maximal benefit can be achieved by dosing at least 10 min prior to meal time.