Dexamethasone pharmacokinetics in Guinea pig inner ear perilymph.
OBJECTIVE
To study the dexamethasone pharmacokinetics in the inner ear perilymph of guinea pigs using high-pressure liquid chromatography.


METHODS
Sixty-five guinea pigs were divided into three groups. In the first group, the drug application protocol used an intra-abdominal dose of 0.5% dexamethasone 4 mg x kg(-1). In the second group, an intratympanic application dose of 0.5% dexamethasone 150 microl was used. The third group was the control group. The concentrations of dexamethasone in inner ear perilymph were determined by high-pressure liquid chromatography.


RESULTS
The perilymph concentration-time curves of dexamethasone conformed to a one-compartment open model after an intra-abdominal application. The Cmax was 0.927 +/- 0.008 mg x l(-1), the Tmax 1.47 +/- 0.04 h, the T(1/2K) 2.92 +/- 0.056 h, the AUC 5.533 +/- 0.05 mg x h x l(-1), the T(1/2Ka) 0.47 +/- 0.024 h. After an intratympanic application, the perilymph concentration-time curves of dexamethasone also conformed to a one-compartment open model. The Cmax was 0.201 +/- 0.006 mg x l(-1), the Tmax 0.117 +/- 0.06 h, the AUC 0.868 +/- 0.004 mg x h x l(-1), the T(1/2K) 2.918 +/- 0.089 h, the T(1/2Ka) 0.161 +/- 0.009 h. Compared to the intra-abdominal application, the intratympanic application resulted in similar levels of inner ear perilymph drug concentrations in 30 min.


CONCLUSIONS
Dexamethasone can penetrate the blood-labyrinthine barrier after intra-abdominal application. Dexamethasone can enter into perilymph after intratympanic application. Under the condition of the study, the intratympanic application resulted in a similar level of inner ear perilymph drug concentrations compared to the intra-abdominal application in 30 min.
Liu
Hong-Jian
HJ
Department of Otorhinolaryngology, Eye and ENT Hospital of Fudan University, Shanghai City, China.
Dong
Ming-Min
MM
Chi
Fang-Lu
FL
D000818:Animals; D002851:Chromatography, High Pressure Liquid; D003907:Dexamethasone / Q000008:administration & dosage / Q000493:pharmacokinetics*; D007758:Ear, Inner; D006168:Guinea Pigs; D010498:Perilymph / Q000378:metabolism*; D011897:Random Allocation
D003907:Dexamethasone