影响住院患者丙戊酸钠血药浓度达标因素的回顾性研究

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。

A retrospective study on factors of standard-reaching rate of valproic acid serum concentration in inpatients

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 in 2016, 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 non-sustained-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.