Influence of Neuroleptics and Benzodiazepines on Metabolism of Tricyclic Antidepressants in Man
LARS F. GRAM M.D.1,
KERSTIN FREDRICSON OVERØ M. PHARM.2, , and
LARS KIRK M.D.3
1 Research Assistant, Psychochemistry Institute, Rigshospitalet, 9, Blegdamsvej, DK-2100 Copenhagen, Denmark
2 Research Assistant, Research Laboratories, H. Lundbeck & Co., Ltd., Valby Copenhagen. Denmark
3 Senior Registrar, Department D, St. Hans Hospital, Roskilde, Denmark
The authors tested the pharmacokinetic interaction between benzodiazepines and nortriptyline in five patients. Each patient was tested during periods of treatment with neuroleptics, diazepam, and chlordiazepoxide, and in a drug-free control period. Neuroleptics (haloperidol and perphenazine) caused changes indicating inhibition of metabolism of 14C-nortriptyline. Neither of the two benzodiazepines caused a significant change in the pharmacokinetic measurements of 14C-nortriptyline. In rats, the metabolism of 14C-nortriptyline was inhibited by pretreatment with chlordiazepoxide, but only when given in a dose of 60 mg./kg. a short time before the administration of 14C-nortriptyline.
