Pharmacokinetics of Hydroxocobalamin in Smoke Inhalation Victims

Houeto, P.; Borron, Stephen W.; Sandouk, P.; Imbert, Michel; Levillain, P.; Baud, Frédéric J.

doi:10.3109/15563659609013809

Cited by 41 publications

(26 citation statements)

References 13 publications

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“…The mean half-life of free and total cob(III)alamins is approximately 26–30 hours after parenteral administration (Houeto et al 1996). A kinetic study in cblC disease patients showed that plasma B 12 levels peaked between 0.5 and 2 hours after administration and fell at a rate of approximately 12 mg/l/hr; the decrease in B 12 levels corresponded with an increase in metabolite levels (Van Hove et al 2002).…”

Section: Managementmentioning

confidence: 99%

Combined methylmalonic acidemia and homocystinuria, cblC type. I. Clinical presentations, diagnosis and management

Carrillo-Carrasco

Chandler

Venditti

2011

J of Inher Metab Disea

191

257

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Combined methylmalonic acidemia and homocystinuria, cblC type, is an inborn error of intracellular cobalamin metabolism with a wide spectrum of clinical manifestations that is stated to be the most common inherited disorder of cobalamin metabolism. This metabolic disease is caused by mutations in the MMACHC gene and results in impaired intracellular synthesis of adenosylcobalamin and methylcobalamin, cofactors for the methylmalonyl-CoA mutase and methionine synthase enzymes. Elevated methylmalonic acid and homocysteine with decreased methionine production are the biochemical hallmarks of this disorder. Awareness of the diverse clinical presentations associated with cblC disease is necessary to provide a timely diagnosis, to guide management of affected individuals and to establish a framework for the future treatment of individuals detected through expanded newborn screening. This article reviews the biochemistry, clinical presentations, genotype-phenotype correlations, diagnosis and management of cblC disease.

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Section: Managementmentioning

confidence: 99%

Combined methylmalonic acidemia and homocystinuria, cblC type. I. Clinical presentations, diagnosis and management

Carrillo-Carrasco

Chandler

Venditti

2011

J of Inher Metab Disea

191

257

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“…Cobalamins (e.g., OH-Cbl) have been used to treat humans with vitamin B 12 deficiency and cyanide poisoning successfully with no or few toxicities [37, 38]. Small doses of OH-Cbl (e.g., 1 mg daily to monthly given orally, intravenously, or intramuscularly) are used to treat vitamin B 12 deficiency, while much larger doses (e.g., 5 to 15 gm intravenously) are used to treat cyanide poisoning [37, 38].…”

Section: Discussionmentioning

confidence: 99%

“…Small doses of OH-Cbl (e.g., 1 mg daily to monthly given orally, intravenously, or intramuscularly) are used to treat vitamin B 12 deficiency, while much larger doses (e.g., 5 to 15 gm intravenously) are used to treat cyanide poisoning [37, 38]. The gram doses used for cyanide poisoning produce transient, mild hypertension as a side effect.…”

Section: Discussionmentioning

confidence: 99%

Inhibition of nitric oxide synthase by cobalamins and cobinamides

Weinberg

Chen

Jiang

et al. 2009

Free Radical Biology and Medicine

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Cobalamins (Cbl) are important co-factors for methionine synthase and methylmalonyl-coA mutase. Certain corrins also bind nitric oxide (NO), quenching its bioactivity. To determine if corrins would inhibit NO synthase (NOS), we measured their effects on 14-C-L-arginine-to-14-C-L-citrulline conversion by NOS1, NOS2, and NOS3. Hydroxocobalamin (OH-Cbl), cobinamide (Cbi), and dicyanocobinamide (CN 2 -Cbi) potently inhibited all isoforms, whfile cyanocobalamin, methylcobalamin, and adenosylcobalamin had much less effect. OH-Cbl and CN 2 -Cbi prevented binding of the oxygen analog carbon monoxide (CO) to the reduced NOS1 and NOS2 heme active site. CN 2 -Cbi did not react directly with NO or CO. Spectral perturbation analysis showed that CN 2 -Cbi interacted directly with the purified NOS1 oxygenase domain. NOS inhibition by corrins was rapid and not reversed by dialysis with L-arginine, tetrahydrobiopterin. Molecular modeling indicated that corrins could access the unusually large heme and substrate-binding pocket of NOS. Best fits were obtained in the "base-off" conformation of the lower axial dimethylbenzimidazole ligand. CN 2 -Cbi inhibited interferon-γ-activated Raw264.7 mouse macrophage NO production. We show for the first time that certain corrins directly inhibit NOS, suggesting that these agents (or their derivatives) may have pharmacological utility. Endogenous cobalamins and cobinamides might play important roles regulating NOS activity in normal and pathological conditions.

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“…We used the hydroxocobalamin apparent volume of distribution of 0.45 L/kg and the maximum therapeutic dose of 10 g in a prototypical 70 kg person to determine that the peak therapeutic serum level of hydroxocobalamin is 317.46 mg/L [(1kg / 0.45L) × (1/70kg) × 10g × (1000mg/1g)=317.46 mg/ L] (2,18). A stock AA00Aaasolution of hydroxocobalamin (Spectrum Chemical Corp., Gardena, CA, USA) at twenty times this peak therapeutic level (20X) was made by dissolving hydroxocobalamin in a 0.9 N NaCl solution (6340 mg/L).…”

Section: Methodsmentioning

confidence: 99%

Spectrophotometry of hydroxocobalamin and hemoglobin reveals production of an unanticipated methemoglobin variant

Denninghoff

Walter

Langa

et al. 2008

Clinical Toxicology

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The remainder spectrum appears to be a methemoglobin variant quantitatively dependant on the amount of hydroxocobalamin added to the hemoglobin solution and the presence of oxygen. The Pearson's correlation coefficient comparing the known swine methemoglobin spectrum with the remainder spectrum reveals a very high degree of correlation (r(2) = 0.986). CONCLUSION. This is the first study to document methemoglobin formation caused by hydroxocobalamin. Further studies are needed in vitro and in vivo to assess this previously unreported methemoglobin variant.

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Pharmacokinetics of Hydroxocobalamin in Smoke Inhalation Victims

Cited by 41 publications

References 13 publications

Combined methylmalonic acidemia and homocystinuria, cblC type. I. Clinical presentations, diagnosis and management

Combined methylmalonic acidemia and homocystinuria, cblC type. I. Clinical presentations, diagnosis and management

Inhibition of nitric oxide synthase by cobalamins and cobinamides

Spectrophotometry of hydroxocobalamin and hemoglobin reveals production of an unanticipated methemoglobin variant

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