【作者】 肖桂荣； 徐珽； 吕晓菊；

【Author】 Xiao Guirong;Xu Ting;Lv Xiaoju;Department of Clinical Pharmacy,West China Hospital of Sichuan University;Center of Infectious Diseases, West China Hospital of Sichuan University;

【机构】 四川大学华西医院临床药学部(药剂科)； 四川大学华西医院感染性疾病中心；

【摘要】 目的:通过伏立康唑血药浓度监测对患者进行个体化药学服务,促进伏立康唑的合理应用。方法:结合临床药师工作实践,总结对伏立康唑血药浓度监测患者的药学服务内容与方法。病例1,女,82岁,35kg,肺曲霉病,于2017年5月12日入院开始静滴注射用伏立康唑200mg q12h,5月16日出现心累,心率160～200次/分,发生药源性阵发性房颤。5月17日查伏立康唑稳态谷浓度20.04 ug˙ml^-1;伏立康唑代谢基因CYP2C19属正常代谢型。5月17日接到医生咨询,告知医生该患者伏立康唑血浓度过高最可能的原因为高龄低体重而药物未减量,建议伏立康唑停药一天后减量至50mg q12h,方案调整2～5天后重新测伏立康唑稳态谷浓度。病例2,男,51岁,57kg,外院HRELfx抗痨3个月胸部CT示无好转,2016年11月7日入院考虑不排除肺真菌病,9日起静滴伏立康唑200mg q12h,11日测伏立康唑谷浓度0.02 ug˙ml-1,伏立康唑代谢基因CYP2C19属正常代谢型。药师分析伏立康唑浓度降低为利福喷丁相互作用所致,建议继续目前方案,1周后复查浓度。病例3,女,71岁,54kg,肺土曲霉病,2016年7月21日起口服伏立康唑200mg bid,后肝酶逐渐升高,9月9日测伏立康唑谷浓度为9.19 ug˙ml^-1,高于上限,测伏立康唑代谢基因CYP2C19*2:AA、CYP2C19*3:GG、CYP2C19*17:CC,属慢代谢型。药师分析伏立康唑基因为慢代谢型,常规剂量给药易致体内药物蓄积,故GGT呈上升的不良趋势,建议伏立康唑剂量减至100mg q12h口服。结果:病例1于5月18日起伏立康唑50mg q12h静滴,23日测伏立康唑稳态谷浓度示4.87ug˙ml^-1,未再出现心脏毒性;病例2于11月22日测伏立康唑谷浓度为2.33 ug˙ml^-1;病例3伏立康唑减量后复查稳态谷浓度为2.78 ug˙ml^-1,以上病例均符合目标浓度范围(1.5～5.5 ug˙ml^-1)。结论:基于血药浓度监测构建医-药-护协作模式,医师严格把握伏立康唑临床应用指征,药师灵活把握血药浓度监测指征,护士准确把握稳态谷浓度取样时间。临床药师关注患者服药方法、合并用药相互作用、药物代谢基因等对伏立康唑血药浓度监测结果的影响,对异常结果进行原因分析并给出方案调整建议,实现个体化药学服务,有利于促进伏立康唑的安全合理使用。更多还原

【Abstract】 OBJECTIVE By monitoring serum concentrations of voriconazole in patients,to promote individualized pharmaceutical care and to improve the rational voriconazole.METHODS: Based on clinical pharmacist’s work practice, the contents and methods of pharmaceutical care were summarized for patients with voriconazole blood concentrations monitored. Patient 1 is a 82-year-old and 39 kilograms female who was diagnosed as pulmonary aspergillosis. The therapy wasvoriconazole 200 mg IV every 12 hours since she was admitted to hospital in May 12, 2017. On May 16, she felt tired heart with heart rate 160～200 beats per min and drug-induced paroxysmal atrial fibrillation was happened to her. On May 17, the trough concentration of voriconazole was 20.04 μg/mL with normal CYP2C19 polymorphiama. The pharmacist was consulted by a doctor onMay 17. According to the pharmacist, the high concentration of voriconazolewas most likely due to the fact that the old age and the low bodyweight of the patientwhile the drug dose has not been reduced. Therefore, the pharmacist suggestedthe voriconazole treatment was discontinued for 24 h and then resumed at the dose of 50 mg IV every 12 hours. The TDM of voriconazole was carried out again after 2～5 days of the adjustment. Patient 2 is a 51-year-old and 57 kilograms male with HRELfxanti-tuberculous therapy for 3 months in other hospital while the Chest CT showed no improvement. He was not get rid of pulmonary mycosis when he was admitted to our hospital in Nov 7, 2016. On Nov 9,the patient began on IV voriconazole 200 mg every 12 hours. The TDM of voriconazole was started on Nov 11 and the trough concentration was 0.02 μg/mL with normal CYP2C19 polymorphiama. The Pharmacist analyzed the voriconazole concentration reduction due to rifapentine interaction and suggested to continue the current treatment and review the concentration after 1 week.Patient 3 is a 71-year-old and 54 kilograms female who diagnosed as pulmonary aspergillusterreus. The patient started to take orally voriconazole 200 mg bid from July 21, 2016. Since then the liver enzymes gradually elevated. The trough concentration of voriconazole was 9.19 μg/mL on Sept 9. The patient was shown to be CYP2C19*2 : AA 、CYP2 C19*3:GG、CYP2C19*17:CC. This genetic profile lead to a slow metabolizing profile.The pharmacist analyzed the drug accumulation in the body increased because of the voriconazole gene as a slow metabolic type so that the GGT was on the rise. The pharmacist suggested to reduce at the dose of 100 mg po every 12 hours.RESULTS:Patient 1 was given to voriconazole 50 mg IV every 12 hours from May 18 and the trough concentration of voriconazole was 4.87 μg/mL on May 23 without cardiac toxicity. Concentration was dramatically elevated with voriconazoletrough of 2.33 μg/mL of Patient 2 on Nov 22. Concentration decreased to 2.78μg/mL of Patient 3. All the Patients were reached the recommended target for TDM(1.5 ～5.5μg/mL).CONCLUSION: Based on the blood concentrationmonitoring to build a doctor-Pharmacist-nurse collaboration model. Doctors strictly grasp the clinical application indications of voriconazole. Pharmacists flexibly catch the indications of blood concentration monitoring.Nurses make the best of the time of blood sampling.Clinical pharmacists needed to pay more attention any factors that could affect results of voriconazole blood concentration, such as methods of taking medicine, drug interactions, drugmetabolism genes. For those with blood concentration beyond the therapeutic range, abnormal results analysis and dosage regimen adjustment suggestion should be carried out. According to the monitoring results of voriconazole blood drug concentration, the clinical pharmacist can carry out individualized pharmaceutical care, which is beneficial to promote safety and rational use of voriconazole.更多还原