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。     

Effect of lanreotide, a somatostatin analogue, on urea synthesis in normal man

The aim was to investigate the effect of lanreotide (Angiopeptin) on urea synthesis. Lanreotide is a somatostatin analogue used in therapy trials of certain cancers. Cancer patients are often protein catabolic, thus the effect of lanreotide on whole body protein metabolism is of importance. We investigated the effect of lanreotide by measuring urea nitrogen synthesis rate (UNSR) and blood alpha-amino nitrogen levels before, during and after a 30 min iv infusion of 25 g of an electrolyte-free amino acid solution. 6 healthy male subjects were studied following, i) placebo (saline), ii) lanreotide 5 mug/kg, and iii) lanreotide 80 mug/kg. Lanreotide decreased urea nitrogen synthesis rate (mmol/h) during amino acid infusion significantly compared to saline, independent of dose of lanreotide (max +/- SE of urea nitrogen synthesis rate measurements in each study: 117 +/- 8 mmol/h (saline), 85 +/- 10 mmol/h (high dose) and 85 +/- 12 mmol/h (low dose)). This occurred in spite of significantly higher plasma alpha-amino nitrogen following lanreotide (peak +/- SE of alpha-amino nitrogen level in each study: 3.7 +/- 0.1 mmol/l placebo versus 4.8 +/- 0.2 mmol/l low dose and 4.7 +/- 0.4 mmol/l high dose (p < 0.01). We conclude that a single dose of lanreotide decreases whole body urea nitrogen synthesis rate thereby conserving body protein. The results indicate that long term lanreotide therapy may not lead to further protein catabolism in cancer patients.     

Circadian variations in serum eosinophil cationic protein, and serum and urine eosinophil protein X

Biochemical evaluation of inflammation may be a useful adjunct to measures of pulmonary function and symptoms in children with asthma. However, little data have been provided to validate the markers in children. The aim of the present study was to assess circadian variations in serum eosinophil cationic protein (ECP), and serum and urine eosinophil protein X (EPX) in children. Five girls and two boys aged 10–14 years were studied. The first sample of urine consisted of urine collected from 24.00 hours the night before until 08.00 hours on the morning of the day of investigation. Thereafter urine was collected at 4-h intervals until 24.00 hours and in another 8-h interval from 24.00 to 08.00 hours. Blood samples for assessment of serum ECP and serum EPX were collected every 2 h during the 24 h. Statistically significant circadian variations in serum ECP (F=3.2, p=0.002), serum EPX (F=3.1, p=0.002) and in urine EPX/creatinine (F=5.4, p=0.003) were detected. The concentrations were higher during the night compared to daytime. Peak levels of serum ECP (mean [± SEM]) were found at 06.00 hours (16.3 [5.3] µg/l), trough levels at 08.00 hours (3.9 [0.7] µg/l) (p=0.01). Peak levels of serum EPX were seen at 06.00 (43.7 [9.5] µg/l) with trough levels at 12.00 hours (22.0 [3.5] µg/l) (p=0.01). Peak levels of urine EPX/creatinine occurred in urine collected from 24.00 to 08.00 hours (90.0 [27.7] µg/mmol), trough levels in the 16.00–20.00 hours sample (29.7 [8.9] µg/mmol) (p=0.02). Serum ECP, serum EPX and urine EPX exhibit a circadian variation in children with nocturnal and early morning peak levels. To avoid confounding influence from circadian variations in ECP and EPX in clinical studies blood or urine should be sampled at consistent times.