两性霉素B治疗艾滋病合并隐球菌性脑膜炎患者的药物浓度研究
Concentrations of amphotericin B in body fluid from patients with AIDS-associated cryptococcal meningitis
摘要目的 测定艾滋病合并隐球菌性脑膜炎(CNM)患者在应用两性霉索B治疗时血液和脑脊髓液中的药物浓度.方法 选择用两性霉素B治疗的艾滋病合并CNM患者10名.在静脉给药达维持剂量后的第7天、第14天和第21天用药前取全血样本.脑脊髓液样本为患者静脉给药达维持剂量l周后每次腰椎穿刺或鞘内给药前留取,通过反向高效液相色谱法测定患者血液和脑脊髓液样品中两性霉素B的浓度.结果 10例患者两性霉素B静脉维持剂量在25~40 mg/d时,其血液稳态谷浓度值范围为1.34~2.27 mg/L,脑脊髓液浓度范围为44.0~91.7μg/L.结论 仅静脉给予两性霉素B或不规则鞘内给药,脑脊髓液中两性霉素B的含量较低,提示应通过增加静脉用药剂量和定期规律鞘内给药来达到理想的浓度值.
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abstractsObjective To determine the concentrations of amphotericin B in serum and cerebrospinal fluid from patients with AIDS-associated cryptococcal meningitis.Methods Ten patients with AIDS-associated cryptococcal meningitis were enrolled in the study.Blood samples were collected before drug administrated at the 7th.14th and 21 th day after maintenance dose achieved.Cerebrospinal fluid samples were collected from lumbar puncture or taken before intrathecal drug administration at least one week after maintenance dose achieved.The concentrations of amphoteriein B in blood and cerebrospinal fluid samples were determined using RP-HPLC.Results When maintenance doses varied from 25 to 40 mg/d,the blood steady-state trough concentration range of amphotericin B was 1.34-2.27 ms/L,and that of cerebrospinal fluid was 44.0-9 1.7μg/L.Conclusions The concentrations of amphotericin B in the cerebrospinal fluid would be lower than the desired concentration if amphotericin B administrated only through intravenous or integrated with irregular intrathecal administration.It suggests that higher dosage of intravenous injection and regular intrathecal administration should be applied to achieve the desired concentration.
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