Sritharan M
Department of Biochemistry, University of Delhi South Campus, India.
Methods Find Exp Clin Pharmacol. 1993 Mar;15(2):107-11.
Clofazimine, a potent antimycobacterial drug, being highly lipophilic accumulates in fatty tissue and in the reticuloendothelial system causing dose-dependent side effects. In this study, the distribution of the free drug and liposome-associated drug was compared after intravenous administration in mice. Differences in the distribution of the drug were observed in the liver, spleen, kidney and lung tissues when injected as free drug and as liposome-associated drug. Following intravenous challenge with the free drug, the drug accumulated quickly and high concentrations of the drug were seen in the spleen, liver, kidney and lung even after 24 h, indicating poor clearance. However, with liposome-associated drug, increased levels were seen in liver, spleen and lung at 1 h with levels falling considerably at 24 h, with no accumulation in the kidney either at 1 h or 24 h after challenge. Clofazimine associated with neutral liposomes was preferentially targetted to spleen and lung, positively charged liposome-associated drug accumulated more in the lungs than in other tissues, while negatively charged liposome-associated drug was directed to liver and spleen. The results suggest that inclusion of clofazimine into liposome not only targets the drug to the organs concerned but also facilitates clearance of the drug, resulting in little accumulation. Also, renal accumulation is much lower as compared to the free drug. This suggests the potential usefulness of liposome as a carrier for clofazimine, thereby reducing the harmful side effects due to excessive accumulation of the drug.
氯法齐明是一种强效抗分枝杆菌药物，因其高度亲脂性而积聚在脂肪组织和网状内皮系统中，会引起剂量依赖性副作用。在本研究中，比较了小鼠静脉注射后游离药物和脂质体结合药物的分布情况。当分别以游离药物和脂质体结合药物形式注射时，在肝脏、脾脏、肾脏和肺组织中观察到了药物分布的差异。静脉注射游离药物后，药物迅速积聚，即使在24小时后，脾脏、肝脏、肾脏和肺中仍能看到高浓度的药物，这表明药物清除率较低。然而，对于脂质体结合药物，在1小时时肝脏、脾脏和肺中的药物水平升高，在24小时时显著下降，在注射后1小时和24小时肾脏中均无药物积聚。与中性脂质体结合的氯法齐明优先靶向脾脏和肺，带正电荷的脂质体结合药物在肺中的积聚比在其他组织中更多，而带负电荷的脂质体结合药物则靶向肝脏和脾脏。结果表明，将氯法齐明包封到脂质体中不仅能使药物靶向相关器官，还能促进药物清除，减少药物积聚。此外，与游离药物相比，肾脏中的积聚要低得多。这表明脂质体作为氯法齐明载体具有潜在的应用价值，从而减少因药物过度积聚而产生的有害副作用。
