3 citations about intranasal cobalamin uptake.

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Cobalamin Nasal Effacity Citations

1)

Gastroenterology. 1997 Aug;113(2):430-3.

Normalization of plasma vitamin B12 concentration by intranasal hydroxocobalamin

in

vitamin B12-deficient patients.

Slot WB, Merkus FW, Van Deventer SJ, Tytgat GN.

Department of Gastroenterology, Academic Medical Center, Amsterdam, The

Netherlands.

BACKGROUND & AIMS: Patients with previous stomach and terminal ileum resections

are

often treated with intramuscular vitamin B12 injections. Disadvantages are, on a

worldwide

scale, the frequent need for medical personnel to administer injections and the

sometimes

painful way of application. This study was designed to investigate the

feasibility of

intranasal hydroxocobalamin suppletion in cobalamin-deficient patients and to

assess

whether intranasal hydroxocobalamin application could be an alternative for

intramuscular

injection. METHODS: Six patients with plasma cobalamin concentrations of < 200

ng/L

were recruited. A dose of 1500 micrograms hydroxocobalamin was applied

intranasally at

days 0, 14, and 21. Plasma cobalamin concentrations were determined 1 hour after

hydroxocobalamin application and on days 0, 7, 21, 28, and 35. RESULTS: All

patients

showed substantial increase of cobalamin concentrations 1 hour after intranasal

application.

In these 6 patients, there was an eightfold increase of mean baseline cobalamin

concentrations. All patients showed a sustained increase of baseline cobalamin

concentrations 1 week after prior intranasal application of hydroxocobalamin. No

side

effects were noted.

CONCLUSIONS: Intranasal application of hydroxocobalamin in cobalamin-deficient

patients

results in fast nasal absorption and leads to sustained increase of baseline

cobalamin

concentrations.

PMID: 9247460 [PubMed - indexed for MEDLINE]

2.)

Br J Clin Pharmacol. 1998 Jan;45(1):83-6.

Nasal absorption of hydroxocobalamin in healthy elderly adults.

van Asselt DZ, Merkus FW, Russel FG, Hoefnagels WH.

Department of Geriatric Medicine, University Hospital Nijmegen, The Netherlands.

AIMS: To investigate the nasal absorption of hydroxocobalamin in 10 healthy

elderly

adults. METHODS: In a cross-over study, blood samples were collected before

administration of the drug and after 10, 20, 30, 40, 60, 120, 180 and 240 min.

The

plasma cobalamin concentration was determined by competitive radioisotope

binding

technique. RESULTS: The maximal plasma cobalamin concentration (Cmax) after

nasal

administration of 750 microg hydroxocobalamin was 1900 +/- 900 pmol l(-1) (mean

+/-

s.d.). The maximal plasma cobalamin concentration was reached in 35 +/- 13 min

(t

[max]). The Cmax after nasal administration of 1500 microg hydroxocobalamin was

3500

+/- 2500 pmol l(-1) with a t(max) of 28 +/- 16 min. Both the AUC(0,240 min) and

AUC

(0,00) increased significantly with an increase of the dose from 750 microg to

1500

microg (P = 0.037 and P = 0.028, respectively). The nasal spray was well

tolerated. No

signs of irritation or local sensitivity were noted.

CONCLUSIONS: The nasal absorption of hydroxocobalamin in healthy elderly adults

is

rapid, high and well tolerated.

PMID: 9489599 [PubMed - indexed for MEDLINE]

3.)

[This one indirectly says that intranasal transport is similarly as effective as

IV]

J Drug Target. 2003 Jul;11(6):325-31.

Hydroxocobalamin uptake into the cerebrospinal fluid after nasal and intravenous

delivery

in rats and humans.

Van den Berg MP, Merkus P, Romeijn SG, Verhoef JC, Merkus FW.

Division of Pharmaceutical Technology and Biopharmaceutics, Leiden/Amsterdam

Center

for Drug Research, Leiden University, P.O. Box 9502 2300 RA Leiden, The

Netherlands.

The possibility of direct transport of hydroxocobalamin from the nasal cavity

into the

cerebrospinal fluid (CSF) after nasal administration in rats was investigated

and the results

were compared with a human study. Hydroxocobalamin was given to rats (n=8) both

intranasally (214 microg/rat) and intravenously (49.5 microg/rat) into the

jugular vein

using a Vascular Access Port (VAP). Prior to and after drug administration,

blood and CSF

samples were taken and analysed by radioimmunoassay. The AUCCSF/AUCplasma ratio

after nasal delivery does not differ from the ratio after intravenous infusion,

indicating that

hydroxocobalamin enters the CSF via the blood circulation across the blood-brain

barrier

(BBB). This same transport route is confirmed by the cumulative AUC-time

profiles in CSF

and plasma, demonstrating a 30 min delay between plasma absorption and CSF

uptake of

hydroxocobalamin in rats and in a comparative human study. The present results

in rats

show that there is no additional uptake of hydroxocobalamin in the CSF after

nasal

delivery compared to intravenous administration, which is in accordance with the

results

found in humans. This indicates a predictive value of the used rat model for the

human

situation when studying the nose to CSF transport of drugs.

PMID: 14668053 [PubMed - indexed for MEDLINE]