Lutsevich A N, Reshet'ko O V, Bogoslovskaia S I
Eksp Klin Farmakol. 1996 May-Jun;59(3):47-52.
Intravenous administration of propranolol (10 mg/kg) to rats with turpentine-induced inflammation and adjuvant-induced arthritis results in the reduction of the systemic clearance (Cltot.p), volume distribution (Vd,ss) and free fraction (fu). At the same time the area under the pharmacokinetic curve (AUC) increases and the half-life period (t1/2 beta) remains the same. In the phenobarbital-treated rats with acute inflammation Cltot.p increases, AUC and t1/2 beta decreased. Administration of cimetidine resulted in the opposite effect. In rats with adjuvant arthritis phenobarbital and cimetidine administration did not affect the propranolol elimination kinetics. In the phenobarbital-treated rats with inflammation Vd,ss significantly decreased and virtually did not change in cimetidine treated rats. The fu of propranolol increased markedly after the cimetidine treatment in all rats with inflammation, whereas phenobarbital treatment appeared effective only in rats with acute inflammation. The tissue-to plasma concentration ratio (Kp) of propranolol decreased in the liver of rats both with acute and chronic inflammation, whereas in the heart the effect was observed only in rats with chronic inflammation. The tissue to plasma concentration ratio of unbound propranolol (Kpu) decreased only in the liver of rats with acute inflammation. In the phenobarbital-treated rats with adjuvant arthritis Kp of propranolol in the liver increased and in the heart decreased, whereas cimetidine-treatment did not change Kp of propranolol in heart and decreased it in the liver. The Kpu of propranolol decreased only in the heart of rats with acute inflammation after phenobarbital treatment, whereas after cimetidine administration this parameter decreased in the heart and in the liver of rats regardless of the character of inflammation.
对松节油诱导炎症和佐剂诱导关节炎的大鼠静脉注射普萘洛尔（10毫克/千克），会导致全身清除率（Cltot.p）、分布容积（Vd,ss）和游离分数（fu）降低。同时，药代动力学曲线下面积（AUC）增加，半衰期（t1/2β）保持不变。在苯巴比妥治疗的急性炎症大鼠中，Cltot.p增加，AUC和t1/2β降低。西咪替丁给药产生相反的效果。在佐剂性关节炎大鼠中，苯巴比妥和西咪替丁给药不影响普萘洛尔的消除动力学。在苯巴比妥治疗的炎症大鼠中，Vd,ss显著降低，而在西咪替丁治疗的大鼠中几乎没有变化。在所有炎症大鼠中，西咪替丁治疗后普萘洛尔的fu显著增加，而苯巴比妥治疗仅在急性炎症大鼠中有效。急性和慢性炎症大鼠肝脏中普萘洛尔的组织与血浆浓度比（Kp）均降低，而仅在慢性炎症大鼠心脏中观察到这种效应。未结合普萘洛尔的组织与血浆浓度比（Kpu）仅在急性炎症大鼠肝脏中降低。在苯巴比妥治疗的佐剂性关节炎大鼠中，肝脏中普萘洛尔的Kp增加，心脏中降低，而西咪替丁治疗不改变心脏中普萘洛尔的Kp，但降低肝脏中的Kp。苯巴比妥治疗后，仅急性炎症大鼠心脏中普萘洛尔的Kpu降低，而西咪替丁给药后，无论炎症性质如何，大鼠心脏和肝脏中的该参数均降低。
