影响住院患者丙戊酸钠血药浓度达标因素的回顾性研究
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摘要
目的:探讨丙戊酸钠的血药浓度与性别、年龄、剂量、剂型、肝肾功能、合用药物等各因素的关系,为调整给药方案提出参考。方法:选取某院2016年1-12月住院期间检测丙戊酸钠血药谷浓度的患者,记录其丙戊酸钠同一剂量满3 d的第一次血药浓度数据,以及在此期间丙戊酸钠的剂量、剂型和患者的性别、年龄、合并用药(肝药酶诱导剂、抑制剂及碳青霉烯类药物)、肝肾功能等信息。规定稳态时的血药浓度在50～100 mg·L~(-1)范围列为达标,利用SPSS软件对数据进行卡方检验或费舍尔精确检验统计单因素影响下的达标率差异。不达标的风险因素分析采用多因素logistic回归模型。P<0.05为差异有统计学意义。结果:该院住院患者丙戊酸钠血药浓度分布大致呈现负偏态分布,且平均值低于达标浓度。非缓释剂组血药浓度达标率(31.67%)低于缓释剂组(51.85%);低剂量组(22.86%)和中间剂量组(45.68%)血药浓度达标率低于高剂量组(64.0%);合用酶诱导剂组血药浓度达标率(20.83%)低于没有合用者(47.86%);合用碳青霉烯类药物者血药浓度达标率(5.56%)低于没有合用者(48.78%),且具有统计学差异。低剂量、中等剂量、非缓释剂型、合用碳青霉烯类药和合用酶诱导剂是住院患者丙戊酸钠血药浓度低于达标浓度的独立风险因素。结论:住院患者丙戊酸钠血药浓度低于达标浓度情况较多,临床药师应根据各个独立风险因素给出剂量调整的建议以及预防措施。
OBJECTIVE To explore the relationship between valproic acid(VPA)serum concentration with age,gender,dosage form,liver and renal function,and concomitant use of some medication,provide a reference to adjustment of medication therapy.METHODS The inpatients were measured for VPA trough serum concentration in our hospital from January to December in2016,and recorded the data of first serum concentration after at least 3 days administration of VPA at the same dose,and the information of age,gender,dosage form,liver and renal function and combination with other medication during the period of medication.The standard concentration was 50-100 mg·L~(-1) in steady state.Chi-square test or Fisher's exact test was used to analyze the single-factor of standard-reaching rate.A multi-logistic regression analysis was used to find independent risk factors for failing to reach the standard serum concentration.RESULTS The data of serum concentration showed a negative skewness distribution and the average value was lower than standard lower limit.Standard-reaching rate of patients used nonsustained-release dosage form(31.67%)was lower than the rate of sustained-release dosage form(51.85%),P=0.017;rates of low-dose(22.86%)and medium-dose(45.68%)were lower than rates of high-dose(64.0%),P=0.005;rate of concomitant use of enzyme inducers(20.83%)was lower than the rate of no concomitant use(47.86%),P=0.015;rate of concomitant use of carbapenems(5.56%)was lower than the rate of no concomitant use(48.78%),P=0.001.And non-sustained-release dosage form,dose,concomitant use of enzyme inducers and carbapenems were independent risk factors of lower than standard serum concentration.CONCLUSION There are many cases that VPA serum concentration is lower than standard concentration in our hospital inpatients.Pharmacists should give advice or preventive measure to make them to become standard according to risk factors showed in the results.
OBJECTIVE To explore the relationship between valproic acid(VPA)serum concentration with age,gender,dosage form,liver and renal function,and concomitant use of some medication,provide a reference to adjustment of medication therapy.METHODS The inpatients were measured for VPA trough serum concentration in our hospital from January to December in2016,and recorded the data of first serum concentration after at least 3 days administration of VPA at the same dose,and the information of age,gender,dosage form,liver and renal function and combination with other medication during the period of medication.The standard concentration was 50-100 mg·L~(-1) in steady state.Chi-square test or Fisher's exact test was used to analyze the single-factor of standard-reaching rate.A multi-logistic regression analysis was used to find independent risk factors for failing to reach the standard serum concentration.RESULTS The data of serum concentration showed a negative skewness distribution and the average value was lower than standard lower limit.Standard-reaching rate of patients used nonsustained-release dosage form(31.67%)was lower than the rate of sustained-release dosage form(51.85%),P=0.017;rates of low-dose(22.86%)and medium-dose(45.68%)were lower than rates of high-dose(64.0%),P=0.005;rate of concomitant use of enzyme inducers(20.83%)was lower than the rate of no concomitant use(47.86%),P=0.015;rate of concomitant use of carbapenems(5.56%)was lower than the rate of no concomitant use(48.78%),P=0.001.And non-sustained-release dosage form,dose,concomitant use of enzyme inducers and carbapenems were independent risk factors of lower than standard serum concentration.CONCLUSION There are many cases that VPA serum concentration is lower than standard concentration in our hospital inpatients.Pharmacists should give advice or preventive measure to make them to become standard according to risk factors showed in the results.
引文
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[12]Wu DL,Chen ZG,Dou WQ,et al.Influence of nasal feeding on serum concentration of valproic acid[J].Herald Med(医药导报),2013,32(2):258-260.
[13]Marahatta A,Bhandary B,Jeong SK,et al.Soybean greatly reduces valproic acid plasma concentrations:a food-drug interaction study[J].Sci Rep,2014,4:4362.
[14]Cao F,Chen YM.Monitoring the concentration of valproic acid and its clinical sense[J].Chin J Drug Appl Monit(中国药物应用与监测),2005,2(6):23-25.
[15]Liu ZJ,Han HL.Drug-drug Interation and Clinic(药物相互作用基础与临床)[M].1st version.Beijing:People's Medical Publishing House,2009.108.
[16]Zeng Y,Liu LL,Yan SY.Analysis of liver function and blood routine of the patients with sodium valproate serum concentration above 90μg·mL-1[J].Chin J Drug Appl Monit(中国药物应用与监测),2013,(2):66-70.
[2]Qiao XY,Qian Q,Wang J.Analysis of related factors between the serum concentrations of sodium valproate and its effectiveness[J].Pharm Care Res(药学服务与研究),2011,11(6):447-449.
[3]Peng M,Deng N.Analysis of Blood Concentration of Sodium Valproate and Its Influential Factors[J].J China Pharm(中国药房),2013(26):2422-2424.
[4]May T,Rambeck B.Serum concentrations of valproic acid:influence of dose and comedication[J].Ther Drug Monit,1985,7(4):387-390.
[5]China Association Against Epilepsy.Clinical Diagnosis and Treatment Guide.Epilepsy Section(临床诊疗指南.癫痫病分册)[M].2nd Ver(2015).Beijing:People's Medical Publishing House,2015:39.
[6]Liu LL,Zeng Y.Clinical analysis on blood concentration of sodium valproate[J].Pract Pharm Clin Remed(实用药物与临床),2013,16(5):429-432.
[7]Zhang J,Zhang H J.Analysis on serum concentration of valproic acid sodium and its influencing factors in the elderly patients with epilepsy[J].Strait Pharm J(海峡药学),2015,(5):247-249.
[8]Li LQ.Monitoring and analysis of plasma concentration of sodium valproate in the treatment of epilepsy[J].Chin J Clin Pharmacol(中国临床药理学杂志),2013,29(8):631-632.
[9]Spriet I,Goyens J,Meersseman W,et al.Interaction between valproate and meropenem:a retrospective study[J].Ann Pharmacother,2007,41(7):1130-1136.
[10]Perucca E,Dulac O,Shorvon S,et al.Harnessing the clinical potential of antiepileptic drug therapy:dosage optimisation[J].CNS Drugs,2001,15(8):609-621.
[11]He XS,Liao W P,Deng Y H,et al.Comparison of the valproate plasma levels and clinical efficacy in patients with epilepsy between conventional preparations and sustained-release preparations of sodium valproate[J].Chin J Pract Intern Med(中国实用内科杂志),2003,23(7):415-416.
[12]Wu DL,Chen ZG,Dou WQ,et al.Influence of nasal feeding on serum concentration of valproic acid[J].Herald Med(医药导报),2013,32(2):258-260.
[13]Marahatta A,Bhandary B,Jeong SK,et al.Soybean greatly reduces valproic acid plasma concentrations:a food-drug interaction study[J].Sci Rep,2014,4:4362.
[14]Cao F,Chen YM.Monitoring the concentration of valproic acid and its clinical sense[J].Chin J Drug Appl Monit(中国药物应用与监测),2005,2(6):23-25.
[15]Liu ZJ,Han HL.Drug-drug Interation and Clinic(药物相互作用基础与临床)[M].1st version.Beijing:People's Medical Publishing House,2009.108.
[16]Zeng Y,Liu LL,Yan SY.Analysis of liver function and blood routine of the patients with sodium valproate serum concentration above 90μg·mL-1[J].Chin J Drug Appl Monit(中国药物应用与监测),2013,(2):66-70.