Effect of Administration Route on the Pharmacokinetics of Cobalamin in Elderly Patients: A Randomized Controlled Trial

Abstract

BackgroundThe gold standard for cobalamin deficiency treatment is administration of cobalamin by intramuscular injection. The injection is painful and inconvenient, particularly for elderly persons. Cobalamin might also be administered intranasally. Previous studies do not provide insight into the pharmacokinetics of intranasal cobalamin administration in comparison with cobalamin injection.AimTo quantify the pharmacokinetics of intranasally and intramuscularly administered cobalamin to determine if intranasal administration might be an alternative for intramuscular administration.MethodsTen inpatients and outpatients of a geriatrics unit were recruited and randomly assigned to receive a single dose of 1000 μg cobalamin administered either by intranasal spray or intramuscular injection (5 per group). Inclusion criteria were written informed consent, age >65 years, and a cobalamin serum concentration <200 pmol/L. Total cobalamin serum concentrations were determined 10 times within 48 hours after administration. The differences in Cmax, Tmax, and AUC0–48 h per administration route were statistically compared using ANOVA.ResultsThe average Cmax was 1 nmol/L after intranasal and 38.5 nmol/L after intramuscular administration. The average Tmax for intranasal and intramuscular administration was 42 minutes versus 342 minutes, respectively, and the AUC0–48 h was 1.3 µmol/L/min versus 45.4 µmol/L/min, respectively. These values also differed significantly (P<0.05). The estimated bioavailability of the intranasal administration was 2%.ConclusionsThe pharmacokinetics of intranasal and intramuscular cobalamin administration in elderly, cobalamin-deficient patients differ significantly. However, the estimated 2% bioavailability of cobalamin after intranasal administration makes intranasal cobalamin administration a potentially interesting administration route for elderly patients. Netherlands Trial Registry identifier: NTR 3005.

Rapidly dissolving bilayer microneedle arrays – A minimally invasive transdermal drug delivery system for vitamin B12

“…This study represents a proof of concept for the feasibility of using rapidly dissolving MN arrays for transdermal delivery of vitamin B12. Predicting pharmacokinetics in humans on the basis of animal studies requires further investigation, especially as pharmacokinetic results for elderly people presented by Tillemans et al (2014) demonstrated considerable differences compared to results obtained in the present study. Nevertheless, the patch size necessary to deliver therapeutically relevant amounts of vitamin B12 can be cautiously extrapolated from the data presented here.…”

Current Nanocarrier Strategies Improve Vitamin B12 Pharmacokinetics, Ameliorate Patients’ Lives, and Reduce Costs

“…To overcome these issues and concerns, recently, intranasal and sublingual VitB12 administrations are being developed and are emerging as being very effective due to their stressless nature. The comparison between intranasal and intramuscular prescription lacks big studies and the available data suggest that intranasal administration has a low bioavailability (between 2% and 5%) which is an appropriate quantity to fulfil the deficiency [ 60 , 61 ]. We must add that in Tillemans’s study, they used hydroxocobalamin solution for injection and cyanocobalamine for spray; these VitB12 forms persist differently in the body and can underestimate the intranasal administration [ 50 , 61 ].…”

Systematic Review and Pragmatic Clinical Approach to Oral and Nasal Vitamin B12 (Cobalamin) Treatment in Patients with Vitamin B12 Deficiency Related to Gastrointestinal Disorders

“…route (more rarely intravenous) have also been developed in the setting of B12 deficiency, as the nasal route [ 35 ]. This route of administration of B12 has seen a revival of interest in recent years [ 36 , 37 , 38 , 39 ]. This renewed interest is mainly due to the development of several commercial forms of intra-nasal spray-dried powders or nasal gel of cyanocobalamin.…”

“…To our knowledge, only one recent study (quiet of poor methodological quality) has documented the clinical utility of the nasal vitamin B12 replacement, with regards to pharmacokinetics, efficacy, and safety [ 39 ]. In this study, the estimated cobalamin bioavailability after intranasal administration was 2%.…”