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

Abstract

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%-x-hours for those receiving a meal at 18.00 h, compared with -238%-x-hours for fasting subjects. The Dunnett-adjusted difference between these two treatment sequences was 147%-x-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.

Figure 1

Time course of plasma salmon calcitonin (sCT) in each meal and treatment sequence in the 2 h following dosing with one single dose of 0.8 mg of oral sCT at 22.00 h. Values given are geometric mean ± 1 SEM. I: Meal at 18:00 (—○—); II: Meal at 20:00 (—◊—); III: Meal at 21:00 (); IV: Meal at 22:10 (--○--); V: No meal (—•—); VI: Placebo (--□--)

Figure 2

Time course of serum C-terminal telopeptide of collagen type I (CTX-I) in the 4 h following one single dose of 0.8 mg of oral salmon calcitonin (sCT) in each treatment sequence. (A) The value relative to predose value; (B) serum CTX-I in absolute levels. Values given are geometric mean ± 1 SEM. I: Meal at 18:00 (—○—); II: Meal at 20:00 (—◊—); III: Meal at 21:00 (); IV: Meal at 22:10 (--○--); V: No meal (—•—); VI: Placebo (--□--)

Figure 3

AUC of relative change (A) and absolute change (B) in serum C-terminal telopeptide of collagen type I (CTX-I) in the 4 h following one single dose of 0.8 mg of oral salmon calcitonin (sCT) in each treatment sequence. Values given are mean ± 1 SEM. Analysis of variance (i–ii–iii–iv–v) of panel A: P < 0.001