Optimizing bioavailability of oral administration of small peptides through pharmacokinetic and pharmacodynamic parameters: The effect of water and timing of meal intake on oral delivery of Salmon Calcitonin

The study was a randomized, partially-blind, placebo-controlled, single dose, exploratory crossover phase I study. 56 healthy postmenopausal women were randomly assigned to receive five treatments. The treatments comprised a combination of study medication (SMC021 (0.8 mg sCT + 200 mg 5-CNAC), SMC021 placebo, or 200 IU Miacalcic？ NS nasal spray), water volume given with the tablet (50 or 200 ml water), and time between dosing and meal (10, 30, or 60 minutes pre-meal). Plasma sCT levels and changes in the bone resorption (C-terminal telopeptide of collagen type I) was investigated. Trial regristrationOral delivery of 0.8 mg of sCT with 50 ml of water compared to that with 200 ml water resulted in a two-fold increase in maximum concentration (Cmax and AUC0–4) of plasma sCT but comparable time to reach maximum concentration (Tmax). The sCT AUC0–4 with 50 ml of water was 4-fold higher than that obtained with nasal calcitonin. The increased absorption of sCT resulted in increased efficacy demonstrated by AUC of the relative change of serum CTX-I measured in the 6 hours post dosing.0.8 mg sCT with 50 ml of water taken 30 and 60 minutes prior to meal time resulted in optimal pharmacodynamic and pharmacokinetic parameters. The data suggest that this novel oral formulation may have improved absorption and reduction of bone resorption compared to that of the nasal form.Calcitonin is a natural peptide hormone produced by parafollicular cells (C-cells) in the thyroid gland [1,2], which is secreted in response to excess calcium in the serum [3]. Calcitonin was discovered more than 40 years ago [4,5], and possesses potent anti-resorptive effects. Calcitonin binds directly to the calcitonin receptor on osteoclasts which result in a transient reversible inhibition of bone resorption [6].Calcitonin (CT) is approved for the treatment of osteoporosis and other diseases involving accelerated bone turnover [6,7]. Calcitonin treatment has until now been limited to either subcutaneous or