Pharmacokinetics of nicotine in rats after multiple-cigarette smoke exposure
The pharmacokinetics of nicotine and its major metabolites was evaluated in male rats after multiple-cigarette smoke exposure. A smoke-exposure apparatus was used to deliver cigarette smoke to the exposure chamber. The rats were exposed to smoke from a single cigarette every 8 hr for 14 days and to the smoke of a cigarette spiked with radiolabeled nicotine on the 15th day. Blood and urine samples were collected at timed intervals during the 10-min smoke-exposure period of the last cigarette and up to 48 hr thereafter. Nicotine, cotinine, and other polar metabolites were separated by thin-layer chromatography and quantified by liquid scintillation counting. The data were analyzed by computer fitting, and the derived pharmacokinetic parameters were compared to those observed after a single iv injection of nicotine and after a single-cigarette smoke exposure. The results indicated that the amount of nicotine absorbed from multiple-cigarette smoke was approximately 10-fold greater than that absorbed from a single cigarette. Also, unlike the single-cigarette smoke exposure experiment, nicotine plasma levels did not decay monotonically but increased after the 5th hr, and high plasma concentrations persisted for 30 hr. The rate and extent of the formation of cotinine, the major metabolite of nicotine, were decreased as compared with their values following a single-cigarette smoke exposure. It was concluded that nicotine or a constituent of tobacco smoke inhibits the formation of cotinine and may affect the biotransformation of other metabolites. Urinary excretion tended to support the conclusions that the pharmacokinetic parameters of nicotine and its metabolites were altered upon multiple as compared to single dose exposure.
- Research Organization:
- Univ. of Maryland, Baltimore
- OSTI ID:
- 5021261
- Journal Information:
- Toxicol. Appl. Pharmacol.; (United States), Vol. 69:1
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
NICOTINE
METABOLISM
UPTAKE
BLOOD
CHRONIC EXPOSURE
DOSE-RESPONSE RELATIONSHIPS
METABOLITES
RATS
TOBACCO SMOKES
TRACER TECHNIQUES
URINE
AEROSOLS
ALKALOIDS
AMINES
ANIMALS
AUTONOMIC NERVOUS SYSTEM AGENTS
AZINES
AZOLES
BIOLOGICAL MATERIALS
BIOLOGICAL WASTES
BODY FLUIDS
COLLOIDS
DISPERSIONS
DRUGS
HETEROCYCLIC COMPOUNDS
ISOTOPE APPLICATIONS
MAMMALS
MATERIALS
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
PARASYMPATHOLYTICS
PARASYMPATHOMIMETICS
PYRIDINES
PYRROLES
PYRROLIDINES
RESIDUES
RODENTS
SMOKES
SOLS
VERTEBRATES
WASTES
560305* - Chemicals Metabolism & Toxicology- Vertebrates- (-1987)