Heinzow B G, Somogyi A, McLean A J
Arch Int Pharmacodyn Ther. 1987 Mar;286(1):5-14.
A study was conducted on the influence of oral coadministration of hydralazine (H) on the pharmacokinetics of d-propranolol (P) and lidocaine (L) in 6 conscious dogs. They were given an oral solution containing P (2 mg/kg) and L (15 mg/kg) alone or together with 25 mg H. Plasma concentrations of P and L and the metabolites monoethylglycinexylidide (MEGX) and glycinexylidide (GX) were measured by specific HPLC methods. Concomitant administration of H caused a significant (p less than 0.05) increase in P peak concentrations (Cmax, 34 +/- 5: 73 +/- 10 ng/ml) and the area under plasma concentration time curve (AUC, 142 +/- 18: 254 +/- 56 ng/ml X hr) of P with significant (p less than 0.05) 24% reduction of the apparent oral clearance. The time to reach peak concentrations (Tmax) and the terminal half life (t1/2 beta) were not altered. In contrast to the pattern seen with P the disposition of L was not affected by H. The change in presystemic clearance of P by H cannot be explained by a general underlying mechanism such as an alteration in liver blood flow alone or portal-systemic shunting, since then the pharmacokinetics of L should parallel those of P. It is speculated that other mechanisms, most likely alteration of P metabolism, are primarily responsible for the observed interaction between P and H.
一项关于口服肼屈嗪（H）对6只清醒犬体内d-普萘洛尔（P）和利多卡因（L）药代动力学影响的研究。给它们单独或与25mg H一起口服含P（2mg/kg）和L（15mg/kg）的溶液。通过特定的高效液相色谱法测定P、L以及代谢产物单乙基甘氨酰二甲苯酰胺（MEGX）和甘氨酰二甲苯酰胺（GX）的血浆浓度。同时给予H导致P的峰浓度（Cmax，34±5：73±10ng/ml）和血浆浓度-时间曲线下面积（AUC，142±18：254±56ng/ml·hr）显著（p＜0.05）升高，同时表观口服清除率显著（p＜0.05）降低24%。达到峰浓度的时间（Tmax）和末端半衰期（t1/2β）未改变。与P的情况不同，L的处置不受H影响。H对P的肝首过清除率的改变不能仅用诸如肝血流量改变或门体分流等一般潜在机制来解释，因为那样的话L的药代动力学应该与P平行。据推测，其他机制，很可能是P代谢的改变，是观察到的P与H之间相互作用的主要原因。
