Document Detail

Radiolabeling and dose fixation study of oral alpha-ketoglutarate as a cyanide antidote in healthy human volunteers.
MedLine Citation:
PMID:  20572756     Owner:  NLM     Status:  MEDLINE    
CONTEXT: Radiolabeling and dose fixation study of alpha-ketoglutarate (A-KG). OBJECTIVE: A-KG is a potential oral antidote for cyanide poisoning. Its protective efficacy in animals was best exhibited at a dose of 2.0 g/kg body weight, which when extrapolated to human is very high. The objective of this study was to reduce the dose of A-KG in humans with concomitant increase in its bioavailability, employing pharmacoscintigraphic techniques to assess kinetics in man. MATERIALS AND METHODS: A-KG was radiolabeled with technetium-99m pertechnetate (Tc-99m) and its purity, labeling efficiency, and stability in vitro were determined by instant thin layer chromatography. Time-dependent bio-absorption of the drug in rats and rabbits was assessed by gamma scintigraphy after oral administration of a tracer dose of (99m)Tc-A-KG mixed with nonradioactive A-KG at a concentration of 0.1-2.0 g/kg in the presence or absence of aqueous dilution. Furthermore, scintigraphy and radiometry studies were performed in healthy human volunteers using 5-20 g of A-KG, given in single or split doses followed by different quantity of water. Drug bioavailability was estimated periodically. RESULTS: High radiolabeling (>97%) of A-KG with a stability of 24 h in vitro was obtained. Less than 1% absorption of the drug occurred within 20 min after A-KG was administered in animals at a concentration of 2.0 g/kg body weight. One-tenth reduction in dose increased the bioavailability to 15%. Significant improvement in gastric emptying of the drug was achieved when the drug was administered along with 1-5 mL of water. In humans, two doses of 10 g A-KG given at an interval of 10 min, followed by 300 mL of water, increased the drug bioavailability to 40% as compared to a single dose of 20 g. DISCUSSION: Significant reduction in A-KG dose was achieved in humans as compared to the recommended dose in animals. CONCLUSION: Aqueous dilution improves the bioavailability of A-KG in humans.
Gaurav Mittal; Thakuri Singh; Neeraj Kumar; Aseem Bhatnagar; Rajendra Prasad Tripathi; Rajkumar Tulsawani; Rajagopalan Vijayaraghavan; Rahul Bhattacharya
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Clinical toxicology (Philadelphia, Pa.)     Volume:  48     ISSN:  1556-9519     ISO Abbreviation:  Clin Toxicol (Phila)     Publication Date:  2010 Jul 
Date Detail:
Created Date:  2010-09-20     Completed Date:  2010-10-06     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101241654     Medline TA:  Clin Toxicol (Phila)     Country:  England    
Other Details:
Languages:  eng     Pagination:  509-15     Citation Subset:  AIM; IM    
Institute of Nuclear Medicine and Allied Sciences, Delhi, India.
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MeSH Terms
Administration, Oral
Antidotes / administration & dosage*
Biological Availability
Cyanides / poisoning*
Isotope Labeling
Ketoglutaric Acids / administration & dosage*,  pharmacokinetics
Middle Aged
Technetium / diagnostic use
Reg. No./Substance:
0/Antidotes; 0/Cyanides; 0/Ketoglutaric Acids; 328-50-7/alpha-ketoglutaric acid; 7440-26-8/Technetium

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