Radioimmunoassay for pyridostigmine
Pyridostigmine is a cholinergic drug used for the treatment of myasthenia gravis and for antagonizing the effects of non-depolarizing muscle relaxants. In addition, military organizations in several countries have an active interest in pyridostigmine as a pretreatment compound for nerve agent poisoning. Anti-pyridostigmine antibodies were produced in rabbits using a pyridostigmine analog conjugated to keyhole limpet hemocyanin. These antibodies were used for development of a radioimmunoassay that has a linear standard curve (r2=0.986) ranging from 0.5 to 10.0 ng/ml of pyridostigmine bromide in a 0.1-ml plasma sample. This assay measures pyridostigmine in plasma with better sensitivity and much greater through-put than do current state-of-the-art high-performance liquid chromatography techniques. In addition, only small volumes (100ml) of the plasma samples are required. Plasma levels of pyridostigmine were determined in the rat after intramuscular administration (0.056mg/kg) of pyridostigmine bromide. Estimates of the various pharmacokinetic parameters were calculated using the computer program NONLIN84. The results were as follows: apparent volume of distribution = 1.97 1/kg, absorption rate constant = 0.277 min-1, elimination rate constant = 0.0273 min-1, area under the curve = 1010 ng x min/ml, absorption rate half-life = 2.41 min, elimination rate half-life = 24.8 min, maximal plasma concentration (Cmax) = 21.3 ng/ml and time to Cmax = 9.02 min.
- Research Organization:
- Army Medical Research Inst. of Chemical Defense, Aberdeen Proving Ground, MD (USA)
- OSTI ID:
- 5842684
- Report Number(s):
- AD-A-208149/5/XAB; USAMRICD-P-88-004
- Resource Relation:
- Other Information: Pub. in the Jnl. of Pharmacology and Experimental Therapeutics, Vol. 247, No. 2, 432-438(1988)
- Country of Publication:
- United States
- Language:
- English
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38 RADIATION CHEMISTRY, RADIOCHEMISTRY, AND NUCLEAR CHEMISTRY
ACETYLCHOLINE
PSYCHOTROPIC DRUGS
RADIOIMMUNOASSAY
PYRIDINES
ANTIBODIES
BLOOD PLASMA
BROMIDES
CARBAMATES
CHOLINESTERASE
DRUGS
HYDROXYL RADICALS
METHYL RADICALS
MUSCLES
POISONING
RABBITS
RATS
SAMPLING
VOLUME
ALKYL RADICALS
AMINES
AMMONIUM COMPOUNDS
ANIMALS
AUTONOMIC NERVOUS SYSTEM AGENTS
AZINES
BIOASSAY
BIOLOGICAL MATERIALS
BLOOD
BODY FLUIDS
BROMINE COMPOUNDS
CARBONIC ACID DERIVATIVES
CARBOXYLESTERASES
CARBOXYLIC ACID SALTS
CENTRAL NERVOUS SYSTEM AGENTS
ENZYMES
ESTERASES
ESTERS
HALIDES
HALOGEN COMPOUNDS
HETEROCYCLIC COMPOUNDS
HYDROLASES
IMMUNOASSAY
IMMUNOLOGY
ISOTOPE APPLICATIONS
MAMMALS
MATERIALS
NEUROREGULATORS
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
PARASYMPATHOMIMETICS
QUATERNARY COMPOUNDS
RADICALS
RADIOASSAY
RADIOIMMUNOLOGY
RODENTS
TRACER TECHNIQUES
VERTEBRATES
550200* - Biochemistry
400700 - Radiochemistry & Nuclear Chemistry