Pharmacokinetics of oral cyanocobalamin formulated with sodium N-[8-(2-hydroxybenzoyl)amino]caprylate (SNAC): an open-label, randomized, single-dose, parallel-group study in healthy male subjects.

摘要: Abstract Background Vitamin B12 (cobalamin) deficiency may be caused by inadequate dietary intake of or conditions that result in malabsorption the vitamin. Crystalline vitamin B12, usually form cyanocobalamin, is administered parenterally (ie, intramuscularly) orally for treating states. Intramuscular administration widely accepted as a treatment method. Oral supplementation also used, but it considered to less reliable. Objective This study was conducted compare pharmacokinetics and tolerability 2 oral formulations cyanocobalamin—a marketed cyanocobalamin tablet (immediate-release 5 mg) formulated with proprietary carrier, sodium N-[8-(2-hydroxybenzoyl)amino]caprylate (SNAC)—to establish feasibility using an absorption enhancer improve uptake first clinical cyanocobalamin/SNAC coformulation. Methods An open-label, randomized, single-dose, parallel-group healthy male subjects. Subjects were randomly assigned 1 4 groups: Treatment A subjects (n = 4) received tablets 5-mg 100-mg SNAC part dose range–finding arm included determine provide measurable concentration at all time points when tested available assay; B 6) SNAC; C commercially tablet; D 1-mg IV. completed 3 weeks before treatments B, C, studied. Human serum analyzed chemiluminescence assay Validation procedures established samples could diluted up 100 times without any effects on accuracy precision. The pharmacokinetic properties characterized noncompartmental analysis. absolute bioavailability estimates calculated between (A, C) IV (D) non–baseline-adjusted concentrations well baseline-adjusted concentrations, body weight adjustments. Tolerability evaluated through review monitoring medical history, physical examination findings, concomitant medications, vital signs, laboratory tests (hematology, chemistry, urinalysis values), electrocardiography, adverse events, serious events. Results Twenty subjects, aged 20 45 years, participated this study. Based data from A, selected use C. formulation containing had greater mean than commercial (5.09% vs 2.16%, respectively), AUC0–last values uncorrected baseline, weight, mass index. It reduced Tmax compared (0.5 hours 6.83 hours, respectively). Ke similar (0.028 1/h 0.025 1/h). Comparable results achieved corrected values. tolerated, there no reported Conclusions SNAC, enhancer, provided significantly improved significant decrease small normal formulation. Both tolerated. ClinicalTrials.gov identifier: NCT01311739 .