Dutoit D, Leroux J M, Vaiva G, Mohamed Y, Thomas P, Pommery J, Taret I, Bianchi-Decaix I, Erb F, Goudemand M
Service de Psychiatrie Générale, C.H.R.U, Unité de Soins Normalisés B, Lille.
Therapie. 1994 Jan-Feb;49(1):71-4.
Serum levels of haloperidol and reduced haloperidol as well as the reduced haloperidol/haloperidol ratios were determined in nine acute schizophrenics on oral haloperidol medication and correlated over 21 days with psycho pathology and extra-pyramidal symptom scores. We have investigated red blood cells haloperidol reductase activity in the group of patients. Significant correlations were found between haloperidol plasma levels and positive sub scale for each patient (r = 0.86 and p < 0.01; r = 0.70 and p < 0.05). We found a correlation between red blood cells reductase activity and the improvement of the psychotic anxiety scale (r = 0.64/and p < 0.05; r = 0.67 and p < 0.05), but not with reduced haloperidol/haloperidol ratios in plasma. The knowledge of reductase activity could predict the treatment response in acute schizophrenic patients. We suggest that the reported inter individual and inter ethnic differences in haloperidol and reduced haloperidol and in clinical response and adverse effects may be a reflection of genetic control of the two oxidative pathways mediated by cytochrome P450 isozyme and/or the reductase pathway mediated by haloperidol reductase in individual subject.
测定了9名口服氟哌啶醇的急性精神分裂症患者血清中氟哌啶醇及其还原代谢产物的水平，以及还原代谢产物/氟哌啶醇的比值，并在21天内将其与精神病理学和锥体外系症状评分进行关联分析。我们还研究了该组患者红细胞中氟哌啶醇还原酶的活性。结果发现，每位患者的氟哌啶醇血浆水平与阳性症状分量表之间存在显著相关性（r = 0.86，p < 0.01；r = 0.70，p < 0.05）。我们发现红细胞还原酶活性与精神病性焦虑量表的改善之间存在相关性（r = 0.64，p < 0.05；r = 0.67，p < 0.05），但与血浆中还原代谢产物/氟哌啶醇的比值无关。还原酶活性的信息可以预测急性精神分裂症患者的治疗反应。我们认为，所报道的氟哌啶醇及其还原代谢产物在个体间和种族间的差异，以及临床反应和不良反应的差异，可能反映了个体受试者中由细胞色素P450同工酶介导的两条氧化途径和/或由氟哌啶醇还原酶介导的还原酶途径的遗传控制。
