University Institute of Pharmaceutical Sciences, Panjab University, Chandigarh-160014, India.
Daiichi Sankyo Life Science Research Centre in India, A unit of Daiichi Sankyo India Pharma Pvt Limited, Village Sarhaul, Sector-18, UdyogVihar Industrial Area, Gurgaon-122015, Haryana, India.
Curr Drug Deliv. 2020;17(4):343-347. doi: 10.2174/1567201817666200220121306.
Rifampicin is known to degrade at the acidic pH of the stomach, especially in the presence of isoniazid. Although isoniazid also degrades partially, its degradation is reversible.
Presently, we provide a proof of the fact that the simultaneous oral administration of rifampicin (RIF), upon incorporation into solid lipid nanoparticles (RIF-SLNs), with isoniazid (INH) overcomes its INH-induced degradation and improves its oral bioavailability in rats.
Solid lipid nanoparticles of RIF (RIF-SLNs) were prepared using a novel and patented method. The effect of INH was investigated on bioavailability of RIF both in its free and encapsulated (RIF-SLNs) form, after oral administration to rats.
C and AUC of RIF increased 158 % and 125 %, respectively, upon incorporation into SLNs versus free RIF when combined with INH. The T decreased from 5.67 h to 3.3 h, and the plasma concentration of RIF remained above its MIC (8 μg/ml) at all the tested time points starting with 15 min, when administered as RIF-SLNs in combination with INH.
The results confirm the scope of combining RIF-SLNs with INH to overcome the bioavailability of free RIF when combined with INH, especially in fixed dose combinations.
利福平已知在胃酸的酸性 pH 值下会降解，尤其是在异烟肼存在的情况下。虽然异烟肼也会部分降解，但它的降解是可逆的。
目前，我们提供了一个事实的证据，即同时口服利福平（RIF），在将其纳入固体脂质纳米粒（RIF-SLNs）后，与异烟肼（INH）一起使用，可以克服其 INH 诱导的降解，并提高其在大鼠中的口服生物利用度。
使用一种新颖的专利方法制备 RIF 的固体脂质纳米粒（RIF-SLNs）。研究了 INH 对 RIF 的生物利用度的影响，无论是在游离形式还是在包裹形式（RIF-SLNs）下，在给予大鼠口服后。
当与 INH 结合时，RIF 纳入 SLNs 后 C 和 AUC 分别增加了 158%和 125%。与游离 RIF 相比，T 从 5.67 小时减少到 3.3 小时，当以 RIF-SLNs 与 INH 联合给药时，RIF 的血浆浓度在所有测试时间点都保持在其 MIC（8μg/ml）以上，从 15 分钟开始。
这些结果证实了将 RIF-SLNs 与 INH 结合以克服与 INH 联合使用时游离 RIF 的生物利用度的范围，特别是在固定剂量组合中。
