| Objective: Antipsychotic drugs can cause most of patients with prolactin(PRL) increased, resulting in hyperprolactinemia, as female, the symptoms will appear as lactation, hirsutism, osteoporosis, menstrual disorder, amenorrhea or infertility, and as male, the symptoms will appear as breast development and lactation, impotence, sperm developmental disorders which leads to infertility. These adverse reactions reduce the drugs compliance of the patients and seriously affected the effective cure for psychiatric disorders.Dopamine(DA) is the main inhibitory factor of prolactin. It is combined with dopamine D2 receptor(D2R) which is located on the cell membrane and give the activation of gene transcription which will inhibit the secretion of PRL. As the third generation of atypical antipsychotic drugs, aripiprazole has the dopamine D2 receptor's partial agonist function, by the domestic and foreign research reports, aripiprazole can provide supplementary treatment to hyperprolactinemia that is caused by antipsychotic drugs, but at present there is no reports about the accurate dose of aripiprazole, which can not only treat the mental illness, but also effectively reduce the side effects of other antipsychotic drugs---hyperprolactinemia. Due to this, the purposes of our work are to find out the best serum drug concentration for achieving high curative effect of aripiprazole in combining with the changes of serum levels of dopamine, its D2 receptor and the drops of prolactin.This subject aims to reduce the side effect of drugs to avoid unreasonable combination of drugs, make a reasonable dosing regimen for patients, and provide scientific basis for clinicians to adjust the drug regimen, subsequently achieve the purpose to improve the quality of life of patients with mental illness.Methods:1 Process of experiment: we chose female psychotic patients as our research objects who were between 18 and 60 years old, PRL>60ng/mL, and took stable or maintenancing dose of antipsychotic drugs. The research objects were randomly divided into 2 groups according aripiprazole doses of 5mg/d(the first group) and 10 mg/d(the second group), and all cases in both groups were treated for 4 weeks. The levels of PRL, dopamine and dopamine D2 receptor before and after treatment were respectively measured; Meanwhile, the serum concentration of aripiprazole were also measured at the end of the fourth week.2 Methods for the determination of dopamine: the level of dopamine in serum samples(DA) was measured by sandwich ELISA. The concentration of dopamine(DA) in samples was calculated by referencing the standard curve.3 Methods for the determination of dopamine D2 receptor(D2R): patient's peripheral blood lymphocytes were isolated by lymphocyte separation liquid, and then the whole cell protein of lymphocytes was extracted by the cell lysis solution. Following the concentration of protein measured according the BCA method, the level of dopamine D2 receptor was measured by sandwich ELISA, and the concentration of dopamine D2 R in samples was calculated by referencing the standard curve.4 Method for the determination of PRL: the PRL concentration in serum of patients was measured by chemiluminescence immunoassay analyzer.5 Method for the determination of serum concentration of aripiprazole: firstly, after two step extraction and purification of 1000?l serum, the peak height ratio of analytical peaks and the internal standard chromatographic analyzer was determined by HPLC, finally, the concentration of each measured material in each sample was determined by standard curve.Results:1 Following 4 week-treatments to the two groups, there was no significant difference in the dopamine concentration from pre-treatment and post-treatment in each group, but there was no significant difference between the two groups; However, there was significant difference in dopamine D2 receptor expression both before and after the treatment(statistical results are t=-5.758, P=0.000 and t=-5.311, P=0.000), also between the two groups(t=8.806,P=0.003);2 After 4 weeks, both their PRL concentrations of the two groups showed a significant downward trend, compared with before treatment, with statistical difference(statistical results are t=7.741,P=0.000 and t=10.896, P=0.000); But there were no significant difference between the two groups.3 the serum concentration of aripiprazole for the first group was 37.16+11.79ng/mL, and the second group was 123.51+32.48ng/mL, compared the serum concentration of aripiprazole in the two group, there was very significant difference(t=-9.714,P=0.000).4 the PRL of the third and the eighth subjects in the first group did not change significantly pre- and post-treatment. Their PRL values showed a substantially downward trend when we increased the dose of aripiprazole to 7.5mg/d for 4 weeks, and the blood drug concentrations of aripiprazole were 34.10 ng/mL and 49.82ng/mL. Continuing to increase the dose of aripiprazole to 10mg/d for 4-week-treatment, the PRL concentration showed a continuous slightly downward trend and serum concentrations of aripiprazole in the two groups increased to 67.80 ng/mL and 102.65 ng/mL. Thereby, we think that it is necessary to modify the scope of serum concentration of aripiprazole for the first group, which is to exclude the concentration value from the third and the eighth subjects with the aripiprazole dose of 5mg/d, instead of 7.5mg/d. Thus, the range of the blood drug concentration of aripiprazole is 40.93±7.01ng/mL.Conclusion:1 Both 5mg/d of aripiprazole to the first group and 10mg/d to the second group all promoted the expression of D2 R, and inhibited the synthesis and secretion of PRL in the patients.2 5mg/d of aripiprazole play a similar role with the dose of 10mg/d in decreasing PRL expression.3 The optimal serum drug concentration range of aripiprazole is 40.93± 7.01ng/mL in the treatment of hyperprolactinemia induced by antipsychotic drugs. |
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