Hydroxocobalamin

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Hydroxocobalamin
intravenous
ATC code
Legal status
Legal status
  • US: OTC (by prescription when injectable), not DEA-controlled
Pharmacokinetic data
Protein bindingVery high (90%)
MetabolismPrimarily liver, cobalamins are absorbed in the ileum and stored in the liver.
Elimination half-life~6 days
Identifiers
  • Coα-[α-(5,6-dimethylbenzimidazolyl)]-
    Coβ-hydroxocobamide
JSmol)
  • Cc1cc2ncn(c2cc1C)C9OC(CO)C(OP3(=O)OC(C)CNC(=O)CCC5C4=C(C)C8=NC(=CC7=NC(=C(C)C6=NC(C)(C(N4[Co](O)O3)C5(C)CC(N)=O)C(C)(CC(N)=O)C6CCC(N)=O)C(C)(CC(N)=O)C7CCC(N)=O)C(CCC(N)=O)C8(C)C)C9O
  • InChI=1S/C62H90N13O14P.Co.H2O/c1-29-20-40-41(21-30(29)2)75(28-70-40)56-52(84)53(42(27-76)87-56)89-90(85,86)88-31(3)26-69-49(83)19-15-36-50-32(4)54-58(6,7)34(12-16-43(63)77)38(71-54)22-39-35(13-17-44(64)78)59(8,23-46(66)80)55(72-39)33(5)51-37(14-18-45(65)79)61(10,25-48(68)82)62(11,74-51)57(73-50)60(36,9)24-47(67)81;;/h20-22,28,31,34-37,42,52-53,56-57,76,84H,12-19,23-27H2,1-11H3,(H15,63,64,65,66,67,68,69,71,72,73,74,77,78,79,80,81,82,83,85,86);;1H2/q;+3;/p-3 checkY
  • Key:GTSMWDDKWYUXGH-UHFFFAOYSA-K checkY
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Hydroxocobalamin, also known as vitamin B12a and hydroxycobalamin, is a

vein.[2]

Side effects are generally few.

cobalamin family of compounds.[6][7] It is found in both raw and cooked beef, together with other cobalamins.[8] Hydroxocobalamin, or another form of vitamin B12, are required for the body to make DNA.[7]

Hydroxocobalamin was first isolated in 1949.

generic medication.[2] Commercially it is made using one of a number of types of bacteria.[11]

Medical uses

Hydroxocobalamin at standard conditions is a solid composed of dark red crystals.
Hydroxocobalamin injection USP (1000 μg/mL) is a clear red liquid solution. Shown is 500 μg B-12 prepared for subcutaneous injection.

Vitamin B12 deficiency

Standard therapy for treatment of vitamin B12 deficiency has been intramuscular (IM) or intravenous (IV) injections of hydroxocobalamin (OHCbl), since the majority of cases are due to malabsorption by the enteral route (gut).

metabolic diseases, vitamin B12-deficient patients with tobacco amblyopia due to cyanide poisoning, and patients with pernicious anemia who have optic neuropathy.[13]

In a newly diagnosed vitamin B12-deficient patient, normally defined as when serum levels are less than 200 pg/ml, daily IM injections of hydroxocobalamin up to 1,000 μg (1 mg) per day are given to replenish the body's depleted cobalamin stores. In the presence of neurological symptoms, following daily treatment, injections up to weekly or biweekly are indicated for six months before initiating monthly IM injections. Once clinical improvement is confirmed, maintenance supplementation of B12 will generally be needed for life.[citation needed]

Cyanide poisoning

Hydroxocobalamin is first line therapy for people with cyanide poisoning.[2] Hydroxocobalamin converts cyanide to the much less toxic cyanocobalamin. Cyanocobalamin is renally cleared. The use of hydroxocobalamin became first line due to its low adverse risk profile, rapid onset of action, and ease of use in the prehospital setting.[14]

Injectable hydroxocobalamin

Injection of hydroxocobalamin is used to rectify the following causes of vitamin B12 deficiency (list taken from the drug prescription label published by the

U.S. Food and Drug Administration
)

Pernicious anemia is the most common cause of vitamin B12 deficiency.[15] While it technically refers to anemia caused specifically by autoimmune deficiency of intrinsic factor, it is commonly used to refer to B12-deficient anemia as a whole, regardless of cause.

Side effects

The literature data on the acute toxicity profile of hydroxocobalamin show it is generally regarded as safe with local and systemic exposure. The ability of hydroxocobalamin to rapidly scavenge and detoxify cyanide by chelation has resulted in several acute animal and human studies using systemic hydroxocobalamin doses at suprapharmacological doses as high as 140 mg/kg to support its use as an

intravenous (IV) treatment for cyanide exposure.[16][17]
The US FDA at the end of 2006 approved the use hydroxocobalamin as an injection for the treatment of cyanide poisoning.

The drug causes a reddish discoloration of the urine (chromaturia), which can look like blood in the urine.[18]

Properties

Hydroxocobalamin acetate occurs as odorless, dark-red

pKa of 7.65.[citation needed
]

Mechanism of action

Vitamin B12 refers to a group of compounds called cobalamins that are available in the human body in a variety of mostly interconvertible forms. Together with

myeloid cells. As a cofactor
, cobalamins are essential for two cellular reactions:

Cobalamins are characterized by a

biochemical point of view, two essential enzymatic reactions require vitamin B12 (cobalamin).[19][20]

tetrahydrofolate, the substrate for metabolic steps that require folate. In a state of vitamin B12 deficiency, the cell responds by redirecting folate metabolic pathways to supply increasing amounts of methyltetrahydrofolate. The resulting elevated concentrations of homocysteine and MMA are often found in patients with low serum vitamin B12 and can usually be lowered with successful vitamin B12 replacement therapy. However, elevated MMA and homocysteine concentrations may persist in patients with cobalamin concentrations between 200 and 350 pg/mL.[21]
Supplementation with vitamin B12 during conditions of deficiency restores the intracellular level of cobalamin and maintains a sufficient level of the two active coenzymes: methylcobalamin and deoxyadenosylcobalamin.

References