Mannucci P M, Vicente V, Alberca I, Sacchi E, Longo G, Harris A S, Lindquist A
A. Bianchi Bonomi Hemophilia and Thrombosis Center, University of Milan, Italy.
Thromb Haemost. 1987 Dec 18;58(4):1037-9.
When desmopressin (DDAVP) is given to mild and moderate hemophiliacs intravenously (i.v.) or subcutaneously (s.c.), there is a very large between-patient variability for peak levels of factor VIII coagulant activity (VIII:C). To evaluate whether or not between-patient variability is related to DDAVP levels achieved in plasma, we measured drug levels in 14 hemophilic volunteers (VIII:C 2 to 31 U/dL) who were randomly given 0.3 micrograms/Kg of i.v. or s.c. DDAVP and crossed-over to the other treatment after an interval of 15-30 days. Peak DDAVP levels (Cmax) were higher for i.v. DDAVP (p less than 0.02), times to peak levels (tmax) were shorter for i.v. DDAVP (p less than 0.001). There was no difference between the i.v. and s.c. routes for plasma DDAVP time curve (AUC) and half-life (t 1/2), but there was much larger variability for pharmacokinetic parameters with i.v. than with s.c. DDAVP. Post-DDAVP VIII:C increased 3.4 +/- 1.6 fold (i.v.) and 3.3 +/- 1.3 fold (s.c.) over baseline levels, with no significant correlation between peak VIII:C and DDAVP levels for either route of administration. These findings establish the s.c. route of DDAVP administration to be bioequivalent in effect to the i.v. route, albeit with less variability. At the DDAVP dosage used in this study and currently recommended for therapy, the VIII:C response is neither a function of the rate of absorption of the compound nor of the magnitude of its plasma concentration.
给轻、中度血友病患者静脉内（i.v.）或皮下（s.c.）注射去氨加压素（DDAVP）时，VIII因子凝血活性（VIII:C）的峰值水平在患者之间存在很大差异。为了评估患者间的差异是否与血浆中达到的DDAVP水平有关，我们测量了14名血友病志愿者（VIII:C为2至31 U/dL）的药物水平，这些志愿者被随机给予0.3微克/千克的静脉内或皮下DDAVP，并在15 - 30天的间隔后交叉接受另一种治疗。静脉注射DDAVP的峰值DDAVP水平（Cmax）更高（p < 0.02），静脉注射DDAVP达到峰值水平的时间（tmax）更短（p < 0.001）。静脉注射和皮下注射途径在血浆DDAVP时间曲线（AUC）和半衰期（t 1/2）方面没有差异，但静脉注射DDAVP的药代动力学参数的变异性比皮下注射大得多。注射DDAVP后，VIII:C比基线水平增加了3.4 ± 1.6倍（静脉注射）和3.3 ± 1.3倍（皮下注射），两种给药途径的VIII:C峰值与DDAVP水平之间均无显著相关性。这些发现表明，DDAVP的皮下给药途径在效果上与静脉给药途径生物等效，尽管变异性较小。在本研究中使用且目前推荐用于治疗的DDAVP剂量下，VIII:C反应既不是该化合物吸收速率的函数，也不是其血浆浓度大小的函数。
