Effect of administration route on the pharmacokinetics of cobalamin in elderly

Approximately 10-15% of the population aged 65 years and older has cobalamin
(Vitamin B12) deficiency. An even higher prevalence of 30-40% is reported for
malnourished and sick elderly people. Cobalamin serves as a cofactor for
several vital biochemical reactions. If deficient, people may suffer from
anaemia, irreversible neurological damage resulting in cognitive impairment,
and neuropsychiatric disorders. Cobalamin deficiency is due to malabsorption of
food-bound cobalamin or insufficient dietary intake.
Administration of cobalamin by way of intramuscular injection is the gold
standard for cobalamin deficiency treatment. It, however, has several
disadvantages. Injections are painful, injection related adverse reactions may
occur, and health care professionals are usually needed to administer these
injections. The latter increases the costs of the treatment considerably. A
more convenient, safer and cost-effective treatment would, therefore, be
advantageous to both patients and the health care system in general.
Food-bound cobalamin is actively absorbed. In contrast, crystalline
cyanocobalamin administered in capsules is absorbed by way of passive diffusion
although at a relatively low efficiency. Approximately 1% of an oral dose of
crystalline cyanocobalamin is absorbed. Oral administration of cyanocobalamin
is, however, efficacious in normalising serum cobalamin levels.
Oral treatment is not an option in patients that are unable to take oral
medication or patients with severe diarrhoea or vomiting. Dysphagia is a common
condition in the elderly population due to age related pathologic changes or
due to cerebrovascular diseases affecting the swallowing mechanism. Intranasal
administration of cobalamin seems a suitable alternative for both cobalamin
injections and oral administration in elderly.
The absorption of intranasal administered cobalamin was demonstrated in two
studies. In these studies, intranasal administration of cobalamin has not been
compared to intramuscular administered cobalamin. Insight in the
pharmacokinetics of intranasal administered cobalamin in comparison with
intramuscular injection is, however, required to determine the optimal dosage
regimen. In addition, the absorption of intranasal administered cobalamin has
been examined in healthy elderly volunteers and patients with ileal resections
or Crohn*s disease only, though cobalamin deficiency is more prevalent in the
sick and/or malnourished elderly population.
In order to determine a dosage regimen for intranasal administered cobalamin in
elderly patients insight in the pharmacokinetics of intranasal administration
compared to intramuscular administration of cobalamin has to be obtained.
Because there are no published pharmacokinetic data of intramuscular cobalamin
in elderly patients both routes of administration need to be investigated.
In this study we investigate the effects of two routes of administration i.e.
cobalamin administered intranasally and cobalamin administered by
intramuscular injection on the pharmacokinetics as expressed in the standard
parameters AUC48hours, Cmax, Tmax and T1/2 in eldery patients.

Establishing the pharmacokinetics of intranasally and intramuscularly
administered cobalamin in elderly.

A randomized, open, comparative, intervention study.

Randomsation, first cobalamin dose can be administered by the standard
intramuscular injection or by intranasal spray.

Per subject a total of 10 blood samples are collected to assess cobalamin
levels over time. This information is used to calculate the AUC48 hours. All
subjects will be given a peripheral venous catheter (*venflon*) to make the
collection of blood samples less invasive.
Both routes of administration will raise cobalamin serum levels. Cobalamin
serum levels in the intranasal administration group might not be raised to the
same extent as the cobalamin serum levels in the intramuscular administration
group. Normalization of serum cobalamin levels might therefore, take longer in
subjects in the intranasal administration group.
After participating in this study subjects are transferred to standard care and
treatment for cobalamin deficiency.