Department of Tropical Medicine and Gastroenterology, Faculty of Medicine, Assiut University, Egypt.
Br J Clin Pharmacol. 2011 Mar;71(3):411-5. doi: 10.1111/j.1365-2125.2010.03851.x.
The aim of this study was to investigate the effect of rectal ozone on portal vein oxygenation and the pharmacokinetic changes of propranolol in patients with liver cirrhosis.
Fifteen patients with liver cirrhosis were included They were given a fixed oral dose of propranolol 80mg on the morning of day 1 after overnight fasting. Blood samples were collected at fixed time intervals for 24h. Patients were given 12 sessions of rectal ozone of 300ml of 40% ozone/oxygen mixture. On day 14 another oral dose of 80mg propranolol was given and blood samples were collected as on day 1. Plasma concentrations of propranolol were measured by HPLC. Portal vein oxygen tension and saturation were measured before and after rectal ozone.
Plasma concentrations of propranolol were reduced after ozone therapy with pronounced decreases in the maximum plasma concentration and the area under the plasma concentration-time curve. The changes were consistent with a decrease in propranolol bioavailability. There was a decrease in the elimination half-life and mean residence time. Portal vein oxygenation significantly increased after rectal ozone.
The changes in the pharmacokinetics of propranolol probably reflect an increase in the rate and extent of its metabolism resulting from improved portal vein oxygenation attributable to the ozone therapy. The present work highlights that ozone can be an alternative medical measure to improve portal vein oxygenation in liver cirrhosis.
本研究旨在探讨直肠内臭氧对门静脉氧合的影响以及肝硬化患者普萘洛尔药代动力学变化。
纳入 15 例肝硬化患者,在禁食过夜后的第 1 天早晨给予固定剂量的普萘洛尔 80mg 口服。在 24 小时内的固定时间间隔采集血样。患者接受 12 次 300ml 浓度为 40%的臭氧/氧气混合直肠臭氧治疗。第 14 天,再次给予 80mg 普萘洛尔口服,并按第 1 天的方式采集血样。采用 HPLC 法测定普萘洛尔的血浆浓度。直肠内臭氧治疗前后测量门静脉氧分压和饱和度。
臭氧治疗后,普萘洛尔的血浆浓度降低,最大血浆浓度和血浆浓度-时间曲线下面积显著下降。这些变化与普萘洛尔生物利用度降低一致。消除半衰期和平均驻留时间缩短。直肠内臭氧治疗后门静脉氧合明显增加。
普萘洛尔药代动力学的变化可能反映了其代谢率和程度的增加,这归因于臭氧治疗改善了门静脉氧合。本研究强调了臭氧可以作为一种替代的医疗措施,以改善肝硬化患者的门静脉氧合。