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Clozapine and its metabolite clozapine-N-oxide (0.5 mg/kg) were administered intraperitoneally to guinea-pigs. Significant amounts of clozapine were detected in plasma, liver, frontal cortex and caudate after clozapine-N-oxide administration. The amount of clozapine detected in plasma two hours post-administration of N-oxide was approximately 40% of the amount of clozapine after clozapine injection. Tissue concentrations of clozapine in liver, frontal cortex and caudate were greater than plasma concentrations. Clozapine concentrations were almost equivalent in the liver. Clozapine concentrations after N-oxide injection were approximately 40-50% lower compared to clozapine concentrations after clozapine administration in the frontal cortex and caudate. A single dose of clozapine-N-oxide was given to a schizophrenic patient. Clozapine plasma concentrations were detected after N-oxide administration. This study shows that clozapine is formed from its N-oxide metabolite and that a reversible metabolic pathway exists for clozapine and clozapine-N-oxide.
M W Jann, and
Y W Lam, and
W H Chang
February 1985,
Acta pharmacologica et toxicologica,
M W Jann, and
Y W Lam, and
W H Chang
December 1979,
Agents and actions,
M W Jann, and
Y W Lam, and
W H Chang
March 1973,
Berliner und Munchener tierarztliche Wochenschrift,
M W Jann, and
Y W Lam, and
W H Chang
January 1963,
Acta tuberculosea et pneumologica Scandinavica,
M W Jann, and
Y W Lam, and
W H Chang
December 1972,
Polski tygodnik lekarski (Warsaw, Poland : 1960),
M W Jann, and
Y W Lam, and
W H Chang
January 1978,
Circulatory shock,
M W Jann, and
Y W Lam, and
W H Chang
February 2019,
The Journal of pharmacology and experimental therapeutics,
M W Jann, and
Y W Lam, and
W H Chang
December 1972,
Zeitschrift fur Laryngologie, Rhinologie, Otologie und ihre Grenzgebiete,
M W Jann, and
Y W Lam, and
W H Chang
October 1951,
The American journal of physiology,
M W Jann, and
Y W Lam, and
W H Chang
January 1972,
Patologia polska,
