Effect of administration route on the pharmacokinetics of cobalamin in elderly patients: a randomized controlled trial - PubMed (original) (raw)
Effect of administration route on the pharmacokinetics of cobalamin in elderly patients: a randomized controlled trial
Monique P H Tillemans et al. Curr Ther Res Clin Exp. 2014.
Abstract
Background: The 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.
Aim: To quantify the pharmacokinetics of intranasally and intramuscularly administered cobalamin to determine if intranasal administration might be an alternative for intramuscular administration.
Methods: Ten 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.
Results: The 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%.
Conclusions: The 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.
Keywords: cobalamin; elderly; intramuscular; intranasal; pharmacokinetics.
Figures
Figure 1
Concentration-time graphs of patients receiving 1000 μg cobalamin by way of (A) intranasal or (B) intramuscular administration.
Figure 2
Average concentration time curves following intranasal and intramuscular cobalamine administration, respectively. Following intranasal administration, mean (SD) Tmax was 42 (16) minutes, Cmax was 1.0 (0.6) nmol/L, and AUC0-48 hours was 1.3 (0.6) µmol/L/min. Following intramuscular administration, mean (SD) Tmax was 324 (215) minutes, Cmax was 38.5 (20.5) nmol/L, and the AUC0-48 hours was 61 (19) µmol/L/min.
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