Pharmacokinetics and pharmacodynamics of sustained-release implant of goserelin in rats / 中国药理学与毒理学杂志

ABSTRACT

OBJECTIVE Toillustratethepharmacokineticsandpharmacodynamicsofdifferentdos-agesofsustained-releaseimplantofgoserelininrats.METHODS Theratsreceivedasingledoseof sustaineed-release i mplant of goserelin 0.3,0.6 and 1 .2 mg per rat by subcutaneous injection,respec-tively.Concentrations of goserelin and testosterone in plas ma were determined by HPLC-MS/MS.The pharmacokineticparameterswerecalculatedbyWinNonlin6.3.RESULTS Themainpharmacokinetic parameters of the 0.3,0.6 and 1 .2 mg per rat were as fowllowsthe area under the concentration-time curve(AUC0-t)was 770 ±96,1534 ±299 and (3233 ±777)μg·L-1·h,and the maximum plasma con-centration(cmax)was 3.7 ±0.3,6.8 ±2.2 and (1 7.6 ±5.4)μg·L-1 ,respectively.Regression analysis was applied to analyze the relationship between AUC0-t and cmax at different doses and those relative coefficients were 0.942 and 0.923 respectively.AUC0-t and cmax increased with the dose in the range of 0.3-1 .2 mg per rat.As for other main pharmacokinetic parameters (peak time,half life,mean resi-dence time,clearance and apparent volume of distribution),there was no significant difference between the three groups.Testosterone plasma concentration reached the highest level following administration and then kept decreasing to low concentrations.Between 28 d and 35 d,testosterone plas ma concentra-tionslowlyincreasedtothenormallevel.CONCLUSION Pharmacokineticcharacteristicsofsustained-release implant of goserelin in rats show a linear relationship,within the dose range of 0.3-1 .2 mg per rat.The results from pharmacodynamic data show that testosterone does not change in a dose-depend-ent manner at a dose ranging from 0.3 to 1 .2 mg per rat.Testosterone plasma concentration decreases to theoretical castrate level (0.5 μg·L-1 )after 4 d following a dose of 0.6-1 .2 mg per rat.