BIOMAT Database Logo BIOMAT Database Logo

The effect of phenobarbital pretreatment on the antitumor activity of 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU), 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea (CCNU) and 1-(2-chloroethyl)-3-(2,6-dioxo-3-piperidyl-1-nitrosourea (PCNU), and on the plasma pharmacokinetics and biotransformation of BCNU. 1979

V A Levin, and J Stearns, and A Byrd, and A Finn, and R J Weinkam

Many patients being treated for primary and secondary brain tumors receive phenobarbital as an anticonvulsant. The effects of chronic oral administration of phenobarbital on the antitumor activity of BCNU, CCNU and PCNU against the intracerebral 9L tumor in rats were determined. Phenobarbital pretreatment eliminated the antitumor activity of BCNU and reduced the activity of PCNU and CCNU. Pretreatment with phenytoin, sodium methylprednisolone succinate and dexamethasone had little or no effect. Pharmacokinetic data for i.v. BCNU in the plasma of rats showed an increase in drug clearance for phenobarbital pretreated animals, compared to a control group. Larger differences were observed when BCNU was given i.p. The half-life of BCNU in sera from pretreated and control group rats was similar. Finally, the in vitro rate of BCNU disappearance in 9000 X g supernatants and microsomes from the livers of pretreated rats was 5-fold faster than the rate of disappearance of BCNU in supernatants from normal animals. We conclude that the chronic oral administration of phenobarbital induces a change in liver enzymes, which accelerates the clearance of BCNU, thereby reducing the antitumor activity of BCNU and the other nitrosoureas. Phenobarbital pretreatment reduces systemic BCNU toxicity.

UI MeSH Term Description Entries
D007700 Kinetics The rate dynamics in chemical or physical systems.
D008099 Liver A large lobed glandular organ in the abdomen of vertebrates that is responsible for detoxification, metabolism, synthesis and storage of various substances. Livers
D008130 Lomustine An alkylating agent of value against both hematologic malignancies and solid tumors. CCNU,Belustine,Cecenu,CeeNU,NSC-79037,NSC 79037,NSC79037
D008297 Male Males
D008775 Methylprednisolone A PREDNISOLONE derivative with similar anti-inflammatory action. 6-Methylprednisolone,Medrol,Metipred,Urbason,6 Methylprednisolone
D009374 Neoplasms, Experimental Experimentally induced new abnormal growth of TISSUES in animals to provide models for studying human neoplasms. Experimental Neoplasms,Experimental Neoplasm,Neoplasm, Experimental
D009607 Nitrosourea Compounds A class of compounds in which the core molecule is R-NO, where R is UREA. Compounds, Nitrosourea
D010634 Phenobarbital A barbituric acid derivative that acts as a nonselective central nervous system depressant. It potentiates GAMMA-AMINOBUTYRIC ACID action on GABA-A RECEPTORS, and modulates chloride currents through receptor channels. It also inhibits glutamate induced depolarizations. Phenemal,Phenobarbitone,Phenylbarbital,Gardenal,Hysteps,Luminal,Phenobarbital Sodium,Phenobarbital, Monosodium Salt,Phenylethylbarbituric Acid,Acid, Phenylethylbarbituric,Monosodium Salt Phenobarbital,Sodium, Phenobarbital
D010672 Phenytoin An anticonvulsant that is used to treat a wide variety of seizures. It is also an anti-arrhythmic and a muscle relaxant. The mechanism of therapeutic action is not clear, although several cellular actions have been described including effects on ion channels, active transport, and general membrane stabilization. The mechanism of its muscle relaxant effect appears to involve a reduction in the sensitivity of muscle spindles to stretch. Phenytoin has been proposed for several other therapeutic uses, but its use has been limited by its many adverse effects and interactions with other drugs. Diphenylhydantoin,Fenitoin,Phenhydan,5,5-Diphenylhydantoin,5,5-diphenylimidazolidine-2,4-dione,Antisacer,Difenin,Dihydan,Dilantin,Epamin,Epanutin,Hydantol,Phenytoin Sodium,Sodium Diphenylhydantoinate,Diphenylhydantoinate, Sodium
D011916 Rats, Inbred F344 An inbred strain of rat that is used for general BIOMEDICAL RESEARCH purposes. Fischer Rats,Rats, Inbred CDF,Rats, Inbred Fischer 344,Rats, F344,Rats, Inbred Fisher 344,CDF Rat, Inbred,CDF Rats, Inbred,F344 Rat,F344 Rat, Inbred,F344 Rats,F344 Rats, Inbred,Inbred CDF Rat,Inbred CDF Rats,Inbred F344 Rat,Inbred F344 Rats,Rat, F344,Rat, Inbred CDF,Rat, Inbred F344,Rats, Fischer

Related Publications

V A Levin, and J Stearns, and A Byrd, and A Finn, and R J Weinkam
Nitrosoureas: 1,3-bis(2-chloroethyl)-1-nitrosourea (NSC-409962; BCNU) and 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea (NSC-79037; CCNU)--clinical brochure.
December 1968, Cancer chemotherapy reports. Part 3,
V A Levin, and J Stearns, and A Byrd, and A Finn, and R J Weinkam
Pharmacokinetics of nitrosoureas: comparison of 1,3-bis-(2-chloroethyl)-1-nitrosourea (BCNU) and 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea (CCNU) after oral and intravenous administration to rats.
December 1984, Tumori,
V A Levin, and J Stearns, and A Byrd, and A Finn, and R J Weinkam
Relationship of 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) and 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea (CCNU) pharmacokinetics of uptake, distribution, and tissue/plasma partitioning in rat organs and intracerebral tumors.
January 1978, Cancer chemotherapy and pharmacology,
V A Levin, and J Stearns, and A Byrd, and A Finn, and R J Weinkam
A toxicologic comparison of the potency and activity of 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) and 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea (CCNU) in mice and rats.
March 1972, Toxicology and applied pharmacology,
V A Levin, and J Stearns, and A Byrd, and A Finn, and R J Weinkam
The effects of BCNU (1,3-bis(2-chloroethyl)-1-nitrosourea) and CCNU (1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea) on glutathione reductase and other enzymes in mouse tissue.
June 1983, Research communications in chemical pathology and pharmacology,
V A Levin, and J Stearns, and A Byrd, and A Finn, and R J Weinkam
Induction of specific-locus and dominant lethal mutations in male mice by 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) and 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea (CCNU).
October 1997, Mutation research,
V A Levin, and J Stearns, and A Byrd, and A Finn, and R J Weinkam
The lethal activity and repair inhibition capacity of 1-(2-chloroethyl)-3-(2,6-dioxo-3-piperidyl)-1-nitrosourea (NSC 95466, PCNU), a nitrosourea with low carbamoylating activity.
January 1983, Investigational new drugs,
V A Levin, and J Stearns, and A Byrd, and A Finn, and R J Weinkam
1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea (CCNU).
May 1981, IARC monographs on the evaluation of the carcinogenic risk of chemicals to humans,
V A Levin, and J Stearns, and A Byrd, and A Finn, and R J Weinkam
Pharmacological disposition of 1-(2-chloroethyl)-3-(2,6-dioxo-3-piperidyl)-1-nitrosourea in mice.
January 1984, Cancer research,
V A Levin, and J Stearns, and A Byrd, and A Finn, and R J Weinkam
Capillary gas chromatography and thermionic N-P-specific detection of 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) or 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea (CCNU) in stability and pharmacokinetic studies.
April 1988, Pharmaceutical research,
Copied contents to your clipboard!