青蒿琥酯皮肤擦剂在小鼠和兔体内的药代动力学研究

将青蒿琥酯溶于苯二甲酸二甲酯,加适量氨酮制成皮肤擦剂。给兔脱毛后,皮肤涂抹此擦剂25mg/kg后,血药浓度达峰时间平均为2 h,峰浓度平均为1.80μg/ml。药物在兔体内平均驻留时间为3.54 h,清除半衰期约为2.46 h。给小鼠脱毛皮肤涂抹擦剂6.7,31.3和71.4 mg/kg,血药浓度在给药后0.5～4 h达高峰,峰浓度分别为0.82,2.05和7.11μg/ml,体内药物平均驻留时间为3.39,2.79及3.54 h,清除半衰期为2.35,1.93及2.45 h。可见,给兔及小鼠皮肤擦剂后,青蒿琥酯吸收良好,血药浓度维持时间较长。     

The Prospective Assessment of Autonomic Nerve Function by Pupillometry in Adolescents with Type 1 Diabetes Mellitus

The study aimed to compare the longitudinal assessment of autonomic nerve function by computerized infrared pupillometry and standard cardiovascular tests in adolescents with diabetes. Adolescents (n = 150) were assessed at two time points (T1 and T2). The median time interval between assessments was 1.5 (range 0.9–3) years. At T1 the median age was 14.5 (range 8.3–19.5) years and the median duration was 6.5 (range 1.1–16) years. The pupillary variables assessed included the resting pupil diameter, the maximum constriction velocity, and the reflex amplitude of constriction. Heart rate reflexes were assessed in response to deep breathing, the Valsalva manoeuvre, and on standing from a lying position (30/15 ratio). Between visits there was a significant decrease in maximum constriction velocity (6.0 mm s^?1 vs 6.3 mm s^?1, p = 0.0001) and resting pupil diameter (6.2 mm vs 6.3 mm, p = 0.001). At reassessment pupillary abnormalities increased from 32 (21 %) to 45 (30%), with 17 (54 %) of the initial abnormalities persisting. Adolescents with abnormally slow maximum constriction velocity compared to those with normal maximum constriction velocity had a higher glycated haemoglobin (HbA_1c%) at T2 (p = 0.02) and between assessments (p = 0.01). Cardiovascular test abnormalities did not increase between visits and the persistence of initial abnormalities was low (21 %). In summary, pupillometry appears a more sensitive test of autonomic nerve dysfunction in adolescents with diabetes than assessment of cardiovascular reflexes.