Reimann I W, Firkusny L, Antonin K H, Bieck P R
Human Pharmacology Institute, Ciba-Geigy, Tübingen, FRG.
Eur J Clin Pharmacol. 1992;42(2):137-41. doi: 10.1007/BF00278472.
The pressor effect of intravenous tyramine (TYR) and noradrenaline (NA) has been evaluated, respectively, in 157 tests in 19 healthy unmedicated subjects, and in 202 tests in 24 similar subjects, all of whom took part in greater than or equal to 3 test sessions. The pressor dose (PD) that raised systolic blood pressure by 30 mm Hg (PD30) ranged from 2 to 8 mg for TYR, and from 3.5 to 17 micrograms.min-1 for NA. Coefficients of variation ranged from 3 to 47% and from 6 to 38% for TYR and NA, respectively, in the intra-subject comparison. The average inter-subject variation in the TYR PD30 was 22% for 8 females and 30% for 11 males; the corresponding variation in the NA PD30 was 27% (8 females) and 26% (16 males). While the average PD30 for NA was similar for males (10.8 micrograms/min) and females (10.9 micrograms/min), a sex-related difference was found for the PD30 of i.v. TYR: 4.4 mg for 11 males and 3.8 mg for 8 females. Additional results from volunteers who took part in fewer than 3 pressor test sessions supported this observation; PD30 of TYR 4.6 mg in 34 males vs 3.5 mg in 21 females. The large intra- and inter-subject variations in the i.v. TYR and NA pressor test results, and the sex difference in the systolic blood pressure response to i.v. TYR, should be considered in assessing the number and gender of subjects required in studies intended to show "significant" differences in the blood pressure response in amine pressor tests.
分别在19名未用药的健康受试者身上进行了157次试验,以及在24名类似受试者身上进行了202次试验,评估了静脉注射酪胺(TYR)和去甲肾上腺素(NA)的升压作用,所有受试者均参加了不少于3次试验。使收缩压升高30 mmHg的升压剂量(PD),酪胺为2至8 mg,去甲肾上腺素为3.5至17微克·分钟⁻¹。在受试者内比较中,酪胺和去甲肾上腺素的变异系数分别为3%至47%和6%至38%。酪胺PD30的受试者间平均变异在8名女性中为22%,在11名男性中为30%;去甲肾上腺素PD30的相应变异为27%(8名女性)和26%(16名男性)。虽然去甲肾上腺素的平均PD30在男性(10.8微克/分钟)和女性(10.9微克/分钟)中相似,但静脉注射酪胺的PD30存在性别差异:11名男性为4.4 mg,8名女性为3.8 mg。参加少于3次升压试验的志愿者的其他结果支持了这一观察结果;酪胺的PD30在34名男性中为4.6 mg,在21名女性中为3.5 mg。在评估胺类升压试验中血压反应显示“显著”差异的研究所需的受试者数量和性别时,应考虑静脉注射酪胺和去甲肾上腺素升压试验结果中受试者内和受试者间的较大变异,以及静脉注射酪胺时收缩压反应的性别差异。