Marked increase of venlafaxine enantiomer concentrations as a consequence of metabolic interactions: A case report

被引:20
作者
Eap, CB [1 ]
Bertel-Laubscher, R [1 ]
Zullino, D [1 ]
Amey, M [1 ]
Baumann, P [1 ]
机构
[1] Hosp Cery, Dept Univ Psychiat Adulte, Unite Biochim & Psychopharmacol Clin, CH-1008 Prilly Lausanne, Switzerland
关键词
D O I
10.1055/s-2000-7975
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
On three occasions, unusually high trough plasma concentrations of venlafaxine were measured in a patient phenotyped and genotyped as being an extensive CYP2D6 metabolizer and receiving 450 mg/day of venlafaxine and multiple comedications. Values of 1.54 and of 0.60 mg/l of venlafaxine and O-desmethylvenlafaxine, respectively, were determined in the first blood sample, giving an unusually high venlafaxine to O-desmethylvenlafaxine ratio. This suggests an impaired metabolism of venlafaxine to O-desmethylvenlafaxine, and is most likely due to metabolic interactions with mianserin (240 mg/day) and propranolol (40 mg/day). Concentration of (S)-venlafaxine measured in this blood sample was almost twice as high as (R)-venlafaxine ((S)/(R) ratio: 1.94). At the second blood sampling, after addition of thioridazine (260 mg/day), which is a strong CYP2D6 inhibitor, concentrations of venlafaxine were further increased (2.76 mg/l), and concentrations of O-desmethylvenlafaxine decreased (0.22 mg/l). A decrease of the (S)I(R)venlafaxine ratio (- 20%) suggests a possible stereoselectivity towards the (R)-enantiomer of the enzyme(s) involved in venlafaxine O-demethylation at these high venlafaxine concentrations. At the third blood sampling, after interruption of thioridazine, concentrations of venlafaxine and O-desmethylvenlafaxine were similar to those measured in the first blood sample. This case report shows the importance of performing studies on the effects of either genetically determined or acquired deficiency of metabolism on the kinetics of venlafaxine.
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页码:112 / 115
页数:4
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