[In vivo distribution and pharmacokinetics of dexamethasone sodium phosphate thermosensitive in situ gel following intratympanic injection].
OBJECTIVE
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.


METHODS
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.


RESULTS
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.


CONCLUSIONS
DSP thermosensitive in situ gel following IT has significant cochlea-oriented and sustained-release effect.
Chen
Gang
G
Department of Pharmaceutical Sciences, West China School of Pharmacy, Sichuan University, Chengdu 610041, China.
Hou
Shi-xiang
SX
Liu
Jun
J
Luan
Jian-gang
JG
Zhang
Yu
Y
D000287:Administration, Topical; D000818:Animals; D003907:Dexamethasone / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D007758:Ear, Inner / Q000378:metabolism*; D004432:Ear, Middle; D005260:Female; D005782:Gels / Q000008:administration & dosage / Q000493:pharmacokinetics; D008297:Male; D011817:Rabbits; D011897:Random Allocation
D005782:Gels; C004180:dexamethasone 21-phosphate; D003907:Dexamethasone