ABSTRACT
The objective of this paper was to establish a level A in vitro-in vivo correlation (IVIVC) for goserelin acetate extended release microspheres for injection. Three kinds of goserelin acetate microspheres with different release rates were prepared and the critical physicochemical properties, such as drug loading, particle size, glass transition temperature and morphology were characterized. In vitro dissolution test of the prepared goserelin acetate microspheres was performed using sample-and-separate method at 45 ℃ in 5% (v/v) methanol. The morphology of the microspheres and the molecular weight of poly (lactic-co-glycolic acid) (PLGA) of the prepared goserelin acetate microspheres were investigated to research the release mechanism of microspheres. The plasma concentration of goserelin was detected after intramuscular injection of goserelin acetate microspheres to SD rats, and correlated with the in vitro release profiles after processing by percent AUC method. The pharmacokinetic experimental protocol of goserelin acetate microspheres for injection in SD rats was approved by the Animal Ethics Committee of Shandong Luye Pharmaceutical Co., Ltd. The results indicated that the developed sample and separate method was able to detect differences in the release characteristics of the prepared goserelin acetate microspheres, and the in vitro-in vivo correlation of goserelin acetate microspheres was excellent (r > 0.98) and had good predictive ability in SD rats.
ABSTRACT
OBJECTIVE: To investigate therapeutic efficacy of Goserelin acetate sustained-release implants combined with bicalutamide in the treatment of elderly (≥70 years old) prostate cancer patients, and its effects on cognitive function and short-term survival rate. METHODS: A total of 56 prostate cancer patients treated in our hospital from Nov. 2014 to Nov. 2016 were divided into observation group and control group according to random number table, with 28 cases in each group. Observation group was given maximal androgen blokage (MAB) treatment which was Goserelin acetate sustained-release implant (subcutaneous injection of abdominal wall, 3. 6 mg/ times, once) combined with Bicalutamide tablet (orally, 50 mg/times, qd). Control group received surgical castration, and then was given docetaxel (intravenous dripping on 1st day) combined with Prednisone acetate tablets (lst-21st day, orally, 5 mg/time, bid) after surgery for adjuvant therapy. Treatment course of 2 groups lasted for 3 weeks, and all patients were followed up for 12 months. Clinical efficacy, Montreal cognitive function assessment table (MoCA) score, serum prostate specific antigen (PSA) levels and 12-month survival rate were observed in 2 groups. RESULTS: The total response rate of observation group was significantly higher than that of control group, with statistical significance (P<0. 05). Before treatment, there was no statistical significance in MoCA score and serum PSA levels between 2 groups (P>0. 05). After treatment, MoCA scores of 2 groups were decreased significantly, and the observation group was higher than the control group, with statistical significance (P<0. 05). 6 and 12 months after treatment, serum PSA levels of 2 groups were decreased significantly, and the observation group was significantly lower than the control group, with statistical significance (P<0. 05); 12-month survival rate of observation group (92. 86％) was significantly higher than that of control group (64. 29％), with statistical significance (P< 0. 05). CONCLUSIONS: Nonsteroidal anti-androgen drugs show significant therapeutic efficacy for elderly prostate cancer, reduce cognitive function damage, improve serum PSA levels, therapeutic efficacy and short-term survival rate.
ABSTRACT
PURPOSE: Granulomas resulting from the administration of luteinizing hormone-releasing hormone analogues (LH-RH analogues) are thought to be very rare. We report on our clinical experience with injection-site granulomas that result from the administration of LH-RH analogues, and we evaluate the incidence rate of these granulomas. MATERIALS AND METHODS: We used the clinical records of 118 patients who were administered LH-RH analogues in 2005. We describe the clinical data of patients who experienced injection-site granulomas and evaluated the incidence rate. RESULTS: Five patients demonstrated injection-site granulomas due to LH-RH analogue administration. The incidence rate was 4.2% (5 of 118 patients). Most of the granulomas occurred after the first or second administration of 11.25mg of leuprorelin acetate. CONCLUSION: The occurrence of granulomas resulting from the administration of LH-RH analogues was thought to be very rare. Our study, however, revealed a higher incidence rate than expected, especially for leuprorelin acetate.