Chen Gang, Hou Shi-xiang, Liu Jun, Luan Jian-gang, Zhang Yu
Department of Pharmaceutical Sciences, West China School of Pharmacy, Sichuan University, Chengdu 610041, China.
Sichuan Da Xue Xue Bao Yi Xue Ban. 2006 May;37(3):456-9.
To investigate the absorption and distribution of DSP (Dexamethasone sodium phosphate)-loaded thermosensitive in situ gel following IT (intratympanic injection) in guinea pig and provide rationale for clinical application.
DSP-loaded thermosensitive in situ gel was prepared by using poloxamer 407 as matrix. The HPLC assays for the determination of DSP and dexamethasone (Dex) in perilymph (PL), cerebrospinal fluid (CSF) and plasma were developed, respectively. DSP-loaded gel and solution were administered after IT or IV (intravenous injection). PL, CSF and plasma were collected periodically. The concentrations of DSP and Dex were measured by HPLC, and were used to estimate in vivo distribution and pharmacokinetic parameters of Dex in the inner ear.
The AUC (area under curve) and t1/2 of Dex in PL following IT DSP-loaded gel were 593.7- and 28.6-fold higher than those following IV DSP solution. Moreover, DSP-loaded gel following IT extended the mean residence time (MRT) by nearly 5 times, compared with the solution. After IT, the concentration levels of Dex in CSF and plasma were much lower than that in PL.
DSP thermosensitive in situ gel following IT has significant cochlea-oriented and sustained-release effect.
研究豚鼠鼓室内注射载地塞米松磷酸钠（DSP）热敏原位凝胶后的吸收与分布情况，为临床应用提供依据。
以泊洛沙姆407为基质制备载DSP热敏原位凝胶。分别建立了测定外淋巴液（PL）、脑脊液（CSF）和血浆中DSP及地塞米松（Dex）的高效液相色谱法。鼓室内注射或静脉注射后给予载DSP凝胶和溶液。定期采集PL、CSF和血浆。采用高效液相色谱法测定DSP和Dex的浓度，用于评估内耳中Dex的体内分布及药代动力学参数。
鼓室内注射载DSP凝胶后，PL中Dex的曲线下面积（AUC）和半衰期（t1/2）分别是静脉注射DSP溶液后的593.7倍和28.6倍。此外，与溶液相比，鼓室内注射载DSP凝胶使平均驻留时间（MRT）延长了近5倍。鼓室内注射后，CSF和血浆中Dex的浓度水平远低于PL中的浓度。
鼓室内注射DSP热敏原位凝胶具有显著的靶向耳蜗和缓释作用。
