Biomaterial Database

Toxicokinetics of soman stereoisomers after subcutaneous administration to atropinized guinea pigs. 1994

A H Due, and H C Trap, and J P Langenberg, and H P Benschop

TNO Prins Maurits Laboratory, Rijswijk, The Netherlands.

The toxicokinetics of the four stereoisomers of the nerve agent C(+/-)P(+/-)-soman were investigated after subcutaneous administration of a 6 LD50 dose (148 micrograms/kg) to anaesthetized, atropinized, and artificially ventilated guinea pigs. Whereas the relatively nontoxic C(+/-)P(+)-isomers were not detected in blood, the highly toxic C(+/-)P(-)-isomers appeared within 1 min in the general circulation and reached maximum levels of 10-15 ng/ml blood within a period of ca. 7 min. In this absorption phase the blood levels of the C(+)P(-)-isomer lag clearly behind those of the C(-)P(-)-isomer. The blood levels of both C(+/-)P(-)-isomers could be mathematically described using non-linear regression by a three-exponential equation, with one exponential term describing the rapid absorption phase and the other two terms describing distribution and elimination. A comparison with the toxicokinetics of the same isomers upon intravenous administration of the same dose shows that the systemic availability upon subcutaneous administration is in the range of 74-83%. Toxicologically relevant concentrations of the C(+/-)P(-)-isomers prevail almost twice as long after subcutaneous than after intravenous administration. From a toxicokinetic point of view, subcutaneous administration of C(+/-)P(+/-)-soman appears not to be a realistic model for the most relevant route of exposure to C(+/-)P(+/-)-soman in case of chemical warfare, i.e. short term respiratory exposure.

UI	MeSH Term	Description	Entries
D007279	Injections, Subcutaneous	Forceful administration under the skin of liquid medication, nutrient, or other fluid through a hollow needle piercing the skin.	Subcutaneous Injections,Injection, Subcutaneous,Subcutaneous Injection
D008297	Male		Males
D008954	Models, Biological	Theoretical representations that simulate the behavior or activity of biological processes or diseases. For disease models in living animals, DISEASE MODELS, ANIMAL is available. Biological models include the use of mathematical equations, computers, and other electronic equipment.	Biological Model,Biological Models,Model, Biological,Models, Biologic,Biologic Model,Biologic Models,Model, Biologic
D006168	Guinea Pigs	A common name used for the genus Cavia. The most common species is Cavia porcellus which is the domesticated guinea pig used for pets and biomedical research.	Cavia,Cavia porcellus,Guinea Pig,Pig, Guinea,Pigs, Guinea
D000818	Animals	Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA.	Animal,Metazoa,Animalia
D001285	Atropine	An alkaloid, originally from Atropa belladonna, but found in other plants, mainly SOLANACEAE. Hyoscyamine is the 3(S)-endo isomer of atropine.	AtroPen,Atropin Augenöl,Atropine Sulfate,Atropine Sulfate Anhydrous,Atropinol,Anhydrous, Atropine Sulfate,Augenöl, Atropin,Sulfate Anhydrous, Atropine,Sulfate, Atropine
D001682	Biological Availability	The extent to which the active ingredient of a drug dosage form becomes available at the site of drug action or in a biological medium believed to reflect accessibility to a site of action.	Availability Equivalency,Bioavailability,Physiologic Availability,Availability, Biologic,Availability, Biological,Availability, Physiologic,Biologic Availability,Availabilities, Biologic,Availabilities, Biological,Availabilities, Physiologic,Availability Equivalencies,Bioavailabilities,Biologic Availabilities,Biological Availabilities,Equivalencies, Availability,Equivalency, Availability,Physiologic Availabilities
D012999	Soman	An organophosphorus compound that inhibits cholinesterase. It causes seizures and has been used as a chemical warfare agent.	Pinacolyl Methylphosphonofluoridate,Methylphosphonofluoridate, Pinacolyl
D013237	Stereoisomerism	The phenomenon whereby compounds whose molecules have the same number and kind of atoms and the same atomic arrangement, but differ in their spatial relationships. (From McGraw-Hill Dictionary of Scientific and Technical Terms, 5th ed)	Molecular Stereochemistry,Stereoisomers,Stereochemistry, Molecular,Stereoisomer