Verhagen A, Ebels J T, Dogterom A A, Jonkman J H
Paul Scherrer Institute, Villigen, Switzerland.
Eur J Clin Pharmacol. 1995;49(1-2):69-72. doi: 10.1007/BF00192361.
The pharmacokinetics and pharmacodynamics of recombinant human growth hormone (rhGH) were studied after a single subcutaneous dose given by jet-injection, and have been compared with the results obtained after conventional needle-injection. Twelve healthy male volunteers completed an open label, randomised, two-way crossover study, with a 7-day washout period between the two single sc doses. Pharmacokinetic parameters were derived from rhGH concentrations in blood samples collected regularly over 24 h after dosing on Day 1 of each period. To investigate the pharmacodynamics, additional samples were taken for the analysis of somatomedin C (IGF-I) and free fatty acids (FFA). A higher and earlier Cmax was found after jet-injection (ratio (%) jet-injected/needle-injected 124; 90%-confidence interval 108-142). The AUC0-infinity for rhGH were similar (ratio (%) jet-injected/needle-injected 98; 90%-confidence interval 93-103). Both treatments were associated with a significant and similar rise in IGF-I. Both administrations of rhGH were associated with identical rhythmical changes in FFA. The study indicates that jet-injected and needle-injected rhGH are bioequivalent with respect to the amount absorbed. The criterion for bioequivalence is not met for the rate of absorption. It is unlikely that the latter finding will influence the pharmacodynamics of rhGH, since bioequipotency was established for the effect on IGF-I generation. Jet-injection was safe in use and was generally well tolerated.
在通过喷射注射给予单次皮下剂量后，对重组人生长激素（rhGH）的药代动力学和药效学进行了研究，并与传统针头注射后的结果进行了比较。12名健康男性志愿者完成了一项开放标签、随机、双向交叉研究，两个单次皮下剂量之间有7天的洗脱期。药代动力学参数来自于在每个周期第1天给药后24小时内定期采集的血样中的rhGH浓度。为了研究药效学，还采集了额外的样本用于分析生长介素C（IGF-I）和游离脂肪酸（FFA）。喷射注射后发现Cmax更高且更早出现（喷射注射/针头注射的比值（%）为124；90%置信区间为108-142）。rhGH的AUC0-无穷大相似（喷射注射/针头注射的比值（%）为98；90%置信区间为93-103）。两种治疗均与IGF-I的显著且相似的升高有关。两种rhGH给药方式均与FFA的相同节律性变化有关。该研究表明，就吸收量而言，喷射注射和针头注射的rhGH具有生物等效性。吸收速率未达到生物等效性标准。后一发现不太可能影响rhGH的药效学，因为已确定对IGF-I生成的作用具有生物等效性。喷射注射使用安全，总体耐受性良好。
