| Objective:To investigate the effect of different CYP1A2 genotypes and different administration intervals of olanzapine on blood drug concentration and efficacy.Methods:Part I:A total of 109 patients with three types of CYP1A2 genotypes that were diagnosed with ICD-10 schizophrenia were enrolled(33 cases with ultrafast metabolism,44 cases with fast metabolism,and 32 cases with intermediate metabolism).The administration interval of azapine is divided into different groups,which are divided into once-daily group and twice-daily group.Both are given oral olanzapine,the initial dose is 10mg/d,and gradually increase to 20mg/d in 2 weeks.The negative and positive symptom scale(PANSS)was used to assess the patients’mental symptoms.The extrapyramidal side reaction scale(RSESE)and self-compiled table were used to record the adverse reactions.The CYP1A2 genotype was detected before treatment,and the liver was monitored before and during the fourth week of treatment Work,kidney function,blood lipids,blood sugar,electrolytes,prolactin,electrocardiogram and other indicators,the blood concentration of olanzapine was detected at 6 am the next day after4 weeks of treatment.Part II:A total of 23 patients with ICD-10 schizophrenia diagnosis were enrolled.The CYP1A2 genotype was tested.Each genotype was randomly divided into a daily group(administered at 8 pm)according to the dosing interval.In the group twice a day(administration at 8 a.m.and 8 p.m.),olanzapine was started from 10 mg/d after admission.The dosage of the drug was adjusted according to the therapeutic effect.The dosage was stabilized within 2 weeks,and the stable dosage could not exceed 20mg/d..The patient took the medicine stably to reach the steady state of the blood drug concentration.The observation point was taken at 8 pm on the 4th weekend of the medicine.The blood concentration(relative peak concentration)of the patient was measured 0.5 hours before taking the drug(relative trough concentration),2 hours after taking the drug and 10 hours after taking the drug).Results:Part I:1.The blood concentration of olanzapine administered once every day and twice a day was 72.03±22.78ng/ml and 69.62±25.21ng/ml respectively,no significant difference(t=0.522,P>0.05);2.Olanzapine blood concentration points under different CYP1A2 genotypes:ultrafast metabolic type 53.37±19.13ng/ml,fast metabolic type 63.20±13.72ng/ml,intermediate metabolic type 99.04±11.96ng/ml,The difference between each group was significant(F=83.310,P<0.01);3.The effect of different CYP1A2 genotypes on the blood concentration of olanzapine compared with different dosing intervals was not significant(t=0.447,1.078,1.057,P>0.05),the ultra-rapid and fast metabolic plasma concentrations of the dosing interval once a day were 55.13±20.87ng/ml,65.57±16.24ng/ml,no Significant difference(P>0.05),the ultra-fast metabolic type and fast metabolizing blood drug concentration were52.08±18.21ng/ml and 61.03±10.85ng/ml,respectively,with a drug interval of twice a day(P<0.05);4.Comparing the effects of different dosing intervals on the efficacy of different CYP1A2 genotypes,there was no significant difference between the groups(t=0.998,0.686,0.157,P>0.05);5.Dosing interval was twice a day Increased prolactin compared to once a day(the incidence rate was 6.9%twice a day and 25.5%in the group once a day)and dyslipidemia(the incidence rate was 3.4%twice a day and17.6%in the group once a day)the incidence rate was decreased,and the difference was significant(?~2=4.567,5.785,P<0.05),and there was no significant difference in the incidence of other adverse reactions(P>0.05).Part II:1.When the CYP1A2 genotype is an ultra-fast metabolic type,the difference between the highest C/D value and the lowest C/D value in the once-daily group and the twice-daily group is 1.84 and 0.57,respectively;2.When the CYP1A2 genotype is fast-metabolism,the difference between the highest C/D value and the lowest C/D value in the once-daily group and the twice-daily group is 1.41 and 0.43,respectively;3.When the CYP1A2 genotype is an intermediate metabolic type,the difference between the highest C/D value and the lowest C/D value in the once-daily group and the twice-daily group is 0.42 and 0.44,respectively.Conclusion:1.When taking olanzapine at a dose of 20 mg/d,increasing the dosing interval has no effect on clinical efficacy;2.When the CYP1A2 genotype is an intermediate metabolic type,it is recommended that the dose of olanzapine be less than20 mg/d;3.Niazapine administration interval is twice a day can reduce the incidence of two adverse reactions of prolactin elevation and dyslipidemia.4.When the CYP1A2genotype is ultra-fast metabolizing type and fast metabolizing,increasing the olanzapine dosing interval to twice a day can make the blood drug concentration dose ratio(C/D)more stable. |
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