The influence of CYP3A5 polymorphisms on haloperidol treatment in patients with alcohol addiction

Abstract

BackgroundIsoenzymes CYP2D6 and CYP3A4, the activity of which varies widely, are involved in metabolism of haloperidol and may influence its profile of efficacy and safety.ObjectiveThe primary aim of this study was to estimate the relationship between CYP3A5 gene polymorphism, activity of the CYP3A isoenzyme, and the risk of development of adverse drug reactions by haloperidol in patients with alcohol abuse.MethodsSixty-six male alcohol-addicted patients participated in the study. The safety of haloperidol was evaluated by Udvalg for Kliniske Undersogelser Side Effect Rating Scale (UKU) and Simpson–Angus Scale for extrapyramidal symptoms (SAS). The activity of CYP3A was evaluated by determining the concentrations of an endogenous substrate of this isoenzyme (cortisol) and its urinary metabolite (6-beta-hydroxycortisol, 6-B-HC). Genotyping of CYP3A5*3 was performed by real-time polymerase chain reaction with allele-specific hybridization.ResultsThe frequency of A-allele occurrence in Russian population was very poor (2.27%). CYP3A5*3 polymorphism had no influence on safety profile indicators of haloperidol (UKU scale: p=0.55, SAS scale: p=0.64). In addition, there was no statistical significant difference between the values of indexes of the metabolic ratio (6-B-HC/cortisol) in groups with different genotypes of CYP3A5*3: GG 5.00 (3.36; 6.39) vs AG 5.26 (2.10; 6.78) (p=0.902).ConclusionThe frequency of A-allele occurrence of CYP3A5*3 in Russian population is very poor, and it has no high influence on the safety of haloperidol treatment; therefore, there are no reasons to take this polymorphism into account in patients with alcohol addiction who receive haloperidol.

CYP3A and CYP2C19 activity in urine in relation to CYP3A4, CYP3A5, and CYP2C19 polymorphisms in Russian peptic ulcer patients taking omeprazole

“… 18 Studies found 96.6%–97.7% CYP3A5*3 allele frequency in Russians. 19 , 20 We found 95.8% CYP3A5*3 allele frequency in our study of Russian peptic ulcer patients, which corresponds to data 19 , 20 described for Caucasians, and particularly Russians.…”

Effects of CYP2C19*17 Genetic Polymorphisms on the Steady-State Concentration of Diazepam in Patients With Alcohol Withdrawal Syndrome

“…Thus, the biotransformation of each substrate of CYP2C19, including drugs, is increased, as well as the elimination of these substrates. 14 The results of previous studies which were conducted by our research group and focused on investigation of the CYP2D6 15 and CYP3A5 16 genetic polymorphisms confirm the importance, relevance and possibility to investigate the personalized approach to the prescription of BZDs (and specifically diazepam) in such cohort of patients. The objective of our study was to investigate the effect of CYP2C19*17 genetic polymorphisms on the steady-state concentration of diazepam as well as its impact on the efficacy and safety rates of therapy in patients with AWS.…”

The relationship between the CYP2C19*17 genetic polymorphism and the efficacy and safety of diazepam in patients with alcohol withdrawal syndrome

“… òî aeå âðåìÿ ìîaeíî ïðåäïîëîaeèòü, ÷òî ó íîñèòåëåé íåìóòàíòíîãî ãåíîòèïà ïî ïîëèìîðôíîìó ìàðêåðó -806C>T (rs12248560) ãåíà CYP2C19 èìååòñÿ áîëåå âûñîêèé ðèñê ðàçâèòèÿ ÍËÐ íà ôîíå òåðàïèè äèàçåïàìîì. Óñïåøíûå ðåçóëüòàòû ðàíåå ïðîâåäåííûõ íàøåé èññëåäîâàòåëüñêîé ãðóïïîé ðàáîò ïî èç-ó÷åíèþ ôàðìàêîãåíîìíûõ áèîìàðêåðîâ íà ïðèìåðå ïîëèìîðôèçìà ãåíîâ CYP2D6 [27,28,30], CYP3A5 [20,21,25] è ABCB1, êîäèðóþùåãî ãëèêîïðîòåèí P, [26,28,29], à òàêaeå ôàðìàêîìåòàáîëîìíûõ áèîìàðêåðîâ [22][23][24] äëÿ îïòèìèçàöèè ðåaeèìà äîçèðîâàíèÿ ãàëîïåðèäîëà ó ïàöèåíòîâ ñ àëêîãîëüíîé çàâèñèìîñòüþ ïîäòâåðaeäàþò âàaeíîñòü ïåðñîíàëèçèðîâàííîãî ïîäõîäà ê íàçíà÷åíèþ áåíçîäèàçåïèíîâ (è êîíêðåòíî äèàçåïàìà) ó äàííîé êàòåãîðèè ïàöèåíòîâ.…”