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Previous Volume 331:276 July 28, 1994 Number 4 Next

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To the Editor: In their 1991 article on clozapine (March 14, 1991, issue),¹ Drs. Baldessarini and Frankenburg stated, "Other trends noted with clozapine include somewhat (20 to 30 percent) higher plasma levels in women and smokers and up to twofold increases between young and older adults." In the reference² cited for this statement, Haring et al. reported that the plasma levels of clozapine are lower in smokers than in nonsmokers, and higher in older than in younger patients.

Olga Delgado Sanchez, Pharm.D.
M. Carmen Puerta Fernandez, Pharm.D.
Servicio de Ordenacion Farmaceutica
28009 Madrid, Spain

References

1. Baldessarini RJ, Frankenburg FR. Clozapine: a novel antipsychotic agent. N Engl J Med 1991;324:746-754. [Medline]
2. Haring C, Meise U, Humpel C, Saria A, Fleischhacker WW, Hinterhuber H. Dose-related plasma levels of clozapine: influence of smoking behaviour, sex and age. Psychopharmacology (Berl) 1989;99:Suppl:S38-S40.

To the Editor: We thank Drs. Delgado Sanchez and Puerta Fernandez for pointing out that our statement that plasma clozapine concentrations are higher in smokers is incorrect. The concentrations are in fact lower in male (but not female) smokers,¹ because of the well-known ability of smoking to induce hepatic drug-metabolizing enzymes. In the same study, the plasma drug concentrations were higher in older patients, because of a tendency toward slower clearance with advancing age, and in women¹. We recently found the concentrations of clozapine and its major metabolites to be 40 percent higher in nonsmoking women than men, when expressed as a ratio of the concentration (in nanograms per milliliter) to the weight-corrected daily dose (in milligrams per kilogram), despite a 60 percent lower average weight-corrected daily dose in women².

Ross J. Baldessarini, M.D.
Frances R. Frankenburg, M.D.
McLean Hospital
Belmont, MA 02178

References

1. Haring C, Meise U, Humpel C, Saria A, Fleischhacker WW, Hinterhuber H. Dose-related plasma levels of clozapine influence of smoking behaviour, sex and age. Psychopharmacology 1989;99:Suppl:S38-S40.
2. Centorrino F, Baldessarini RJ, Kando JC, Frankenburg FR, Volpicelli SA, Flood JA. Clozapine and metabolites: concentrations in serum and clinical findings during treatment of chronically psychotic patients. J Clin Psychopharmacol 1994;14:119-125. [Medline]

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