Objective: Serious infections or inflammations have been associated with serum clozapine concentration increases and sometimes with clozapine toxicity. Method: These two cases describe Chinese patients (Case 1: a 57-year-old female nonsmoker with severe dermatitis and Case 2: a 47-year-old male nonsmoker with influenza and secondary infection). Results: In both cases, the Drug Interaction Probability Scale established the presence of a probable drug–drug interaction. In both cases, the clozapine and the total clozapine concentration-to-dose ratios followed a temporal pattern (normal–high–normal), consistent with an inhibition of clozapine metabolism during peak inflammation. In the first case, the total clozapine concentration-to-dose ratio (8 with no/low inflammation: median of 3.10 and 2 at peak inflammation: median of 3.90) provided a significant difference (P = 0.044). In the second patient, because of the smaller sample size and reduced statistical power (4 with no infection: a median of 1.59 and 2 at peak infection: 3.46), the increase did not reach significance (P = 0.13). In the first case, the median baseline clozapine concentration-to-dose ratio increased by a factor of 1.45 from 2.00 to a peak of 2.89. To compensate for the inhibition of clozapine metabolism, the dose correction factor was 0.69 (1/1.45) or a decrease in dose of approximately one-third. In the second case, the median baseline clozapine concentration-to-dose ratio increased by a factor of 2.56 from 1.15 to a peak of 2.94. Conclusion: This provided a dose correction factor of 0.40 (1/2.56) or approximately half the dose, similar to published cases in Caucasians with serious respiratory infections.
|Number of pages||14|
|Journal||International Journal of Psychiatry in Medicine|
|State||Published - Jul 1 2018|
Bibliographical noteFunding Information:
The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: The study was financed by three grants to the Beijing Anding Hospital. The principal investigators were Dr Ruan (Capital Medical Research Development Fund of China 2014–2-2122), Dr Guo (Beijing Science and Technology Plan Project Z151100004015180), and Dr Wang (Beijing Municipal Administration of Hospitals Clinical Medicine Development of Special Funding ZY201403).
© 2018, © The Author(s) 2018.
- drug interaction
ASJC Scopus subject areas
- Psychiatry and Mental health