Effects of Caffeine Withdrawal From the Diet on the Metabolism of Clozapine in Schizophrenic Patients
| Autor: | Sara I. Ramos, Angustias G. Herraiz, Julio Benítez, Juan Antonio Carrillo |
|---|---|
| Rok vydání: | 1998 |
| Předmět: |
Adult
Male Psychosis Cytochrome P-450 CYP1A2 Inhibitors Biological Availability Pharmacology chemistry.chemical_compound Pharmacokinetics Cytochrome P-450 CYP1A2 Caffeine medicine Humans Pharmacology (medical) Clozapine Biotransformation Chromatography High Pressure Liquid Psychiatric Status Rating Scales Dose-Response Relationship Drug Chemistry CYP1A2 Metabolism medicine.disease Substance Withdrawal Syndrome Psychiatry and Mental health Schizophrenia Caffeine withdrawal Female Drug Monitoring Antipsychotic Agents medicine.drug |
| Zdroj: | Journal of Clinical Psychopharmacology. 18:311-316 |
| ISSN: | 0271-0749 |
| Popis: | Both clozapine (CLZ) and caffeine are CYP1A2 substrates. This study raises the hypothesis of whether caffeine withdrawal from the diet alters the metabolism and/or clinical status of patients receiving CLZ. Seven schizophrenic patients (six men and one woman) receiving monotherapy with CLZ at 271+/-102 mg/day (3.73+/-1.4 mg/kg) participated in the study. CLZ, norclozapine (NOR), and clozapine-N-oxide (NOX) were assayed in plasma by high-performance liquid chromatography at three different time points: A, with concomitant intake of caffeine from the diet; B, after caffeine withdrawal for 5 days; and C, after 2 weeks of rechallenge to habitual caffeine intake. The CYP1A2 activity was determined by means of a urinary caffeine test. After a caffeine-free diet for 5 days, CLZ concentrations relative to time point A decreased from 486 to 306 ng/mL (-47%) (p0.02), NOX levels decreased from 66 to 49 ng/mL (-31%) (p0.03), and the NOR/CLZ ratio significantly increased from 0.47 to 1.04 (185%) (p0.02). All parameters returned to initial figures at time point C. The NOR/CLZ ratio was significantly correlated to the CYP1A2 index (rs = 0.96, p0.0005). In conclusion, changes in the habitual caffeine intake alter the metabolism of CLZ in schizophrenic patients. Thus, patient intake of caffeine should be medically supervised, and the monitoring of CLZ and metabolite levels may be warranted. Furthermore, in those patients who receive therapy with CLZ, the NOR/CLZ ratio may provide an additional and valuable estimate of CYP1A2 activity. |
| Databáze: | OpenAIRE |
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