Objective： We aimed to evaluate the efficiency of serum testosterone suppression as well as the potential for agonistic stimulation of serum testosterone during chronic treatment with monthly （3.75 mg） depot formul...Objective： We aimed to evaluate the efficiency of serum testosterone suppression as well as the potential for agonistic stimulation of serum testosterone during chronic treatment with monthly （3.75 mg） depot formulation of domestic substitute of leuprorelin acetate microspheres for patients with metastatic prostate cancer. Methods： A total of 23 patients with metastatic prostate cancer were enrolled in the prospective study and received 6 monthly intramuscular depot injections of domestic substitute of leuprorelin acetate microspheres. Their levels and patterns of serum testosterone suppression and the potential for agonistic stimulation of serum testosterone were monitored following injection monthly （3.75 rag） depot formulation of domestic substitute of leuprorelin acetate microspheres for 24 weeks. Results： Mean testosterone was 431.4 ng/dL, 119.3 ng/dL, 28.2 ng/dL by week 1, 2, 3 and decreased to less than 15.6 ng/dL by week 4 where it remained throughout the treatment period. Median time to suppression of serum testosterone was 20.7 days. No transient minor ＂escape＂ from suppression occurred in all patients which was defined as a single testosterone value greater than 50 ng/dL once suppression was achieved. Assessment of agonistic stimulation following the second depot injection revealed no pattern of stimulation. Conclusion： We concluded that monthly （3.75 mg） depot formulation of domestic substitute of leuprorelin acetate microspheres could provide persistent, stable suppression of serum testosterone throughout the dosing intervals, and that the initial depot injection of this formulation also could provide sufficient pituitary desensitization to prevent agnostic stimulation of serum testosterone during chronic treatment.展开更多
Leuprorelin®(LEP) is an FDA drug for breast cancer and prostate cancer treatment. There are several reported adverse effects such as transient hypertension, excessive salivation, and increased dysuria during ...Leuprorelin®(LEP) is an FDA drug for breast cancer and prostate cancer treatment. There are several reported adverse effects such as transient hypertension, excessive salivation, and increased dysuria during treatment with LEP. In this study, the efficacy and toxicity of LEP were modified by using a drug delivery system to adjust the physicochemical properties. In this regard, Leuprorelin®conjugates of triphenylmethanol derivatives (TPMs) were synthesized as prodrugs. Comparative antiproliferative assays showed that LEP-TPMs conjugates had significantly higher antiproliferative activities than the corresponding non-covalent physical mixtures of the TPMs and LEP against human invasive ductal carcinoma (BT-549), human prostate carcinoma (PC3), human lung cancer (A549) and mouse pre-adipocytes (3T3-L1) cells.展开更多
Background：In central precocious puberty （CPP）,the pulse secretion and release ofgonadotropin-releasing hormone （GnRH） are increased due to early activation of the hypothalamic-pituitary-gonadal axis,resulting in...Background：In central precocious puberty （CPP）,the pulse secretion and release ofgonadotropin-releasing hormone （GnRH） are increased due to early activation of the hypothalamic-pituitary-gonadal axis,resulting in developmental abnormalities with gonadal development and appearance of secondary sexual characteristics.The CPP without organic disease is known as idiopathic CPP （ICPP）.The objective of the study was to evaluate the clinical efficacy and safety of domestic leuprorelin （GnRH analog） in girls with ICPP.Methods：A total of 236 girls with ICPP diagnosed from April 2012 to January 2014 were selected and were randomized into two groups.One hundred fifty-seven girls in the test group were treated with domestic leuprorelin acetate,79 girls in the control group were treated with imported leuprorelin acetate.They all were treated and observed for 6 months.After 6-month treatment,the percentage of children with peak luteinizing hormone （LH） ≤3.3 U/L,the percentage of children with peak LH/peak follicle stimulating hormone （FSH） ratio 〈0.6,the improvements of secondary sexual characteristics,gonadal development and sex hormone levels,the change of growth rate of bone age （BA） and growth velocity,and drug adverse effects between two groups were compared.Results：After the treatment,the percentage of children with a suppressed LH response to GnRH,defined as a peak LH ≤3.3 U/L,at 6 months in test and control groups were 96.80% and 96.20%,respectively,and the percentage of children with peak LH/FSH ratio ≤0.6 at 6 months in test and control groups were 93.60% and 93.70%,respectively.The sizes of breast,uterus and ovary of children and the levels of estradiol （E2） were significantly reduced,and the growth rate of BA was also reduced.All the differences between pre-and post-treatment in each group were statistically significant （P 〈 0.05）,but the differences of the parameters between two groups were not significant （P 〉 0.05）.Conclusions：Domestic leuprorelin is effective and safe in the treatment of Chinese girls with ICPP.Its effectiveness and safety are comparable with imported leuprorelin.展开更多
基金Supported by a grant from the State Key Laboratory of Environmental Chemistry and Ecotoxicology,Chinese Academy of Sciences(No.KF2011-12)
文摘Objective： We aimed to evaluate the efficiency of serum testosterone suppression as well as the potential for agonistic stimulation of serum testosterone during chronic treatment with monthly （3.75 mg） depot formulation of domestic substitute of leuprorelin acetate microspheres for patients with metastatic prostate cancer. Methods： A total of 23 patients with metastatic prostate cancer were enrolled in the prospective study and received 6 monthly intramuscular depot injections of domestic substitute of leuprorelin acetate microspheres. Their levels and patterns of serum testosterone suppression and the potential for agonistic stimulation of serum testosterone were monitored following injection monthly （3.75 rag） depot formulation of domestic substitute of leuprorelin acetate microspheres for 24 weeks. Results： Mean testosterone was 431.4 ng/dL, 119.3 ng/dL, 28.2 ng/dL by week 1, 2, 3 and decreased to less than 15.6 ng/dL by week 4 where it remained throughout the treatment period. Median time to suppression of serum testosterone was 20.7 days. No transient minor ＂escape＂ from suppression occurred in all patients which was defined as a single testosterone value greater than 50 ng/dL once suppression was achieved. Assessment of agonistic stimulation following the second depot injection revealed no pattern of stimulation. Conclusion： We concluded that monthly （3.75 mg） depot formulation of domestic substitute of leuprorelin acetate microspheres could provide persistent, stable suppression of serum testosterone throughout the dosing intervals, and that the initial depot injection of this formulation also could provide sufficient pituitary desensitization to prevent agnostic stimulation of serum testosterone during chronic treatment.
文摘Leuprorelin®(LEP) is an FDA drug for breast cancer and prostate cancer treatment. There are several reported adverse effects such as transient hypertension, excessive salivation, and increased dysuria during treatment with LEP. In this study, the efficacy and toxicity of LEP were modified by using a drug delivery system to adjust the physicochemical properties. In this regard, Leuprorelin®conjugates of triphenylmethanol derivatives (TPMs) were synthesized as prodrugs. Comparative antiproliferative assays showed that LEP-TPMs conjugates had significantly higher antiproliferative activities than the corresponding non-covalent physical mixtures of the TPMs and LEP against human invasive ductal carcinoma (BT-549), human prostate carcinoma (PC3), human lung cancer (A549) and mouse pre-adipocytes (3T3-L1) cells.
文摘Background：In central precocious puberty （CPP）,the pulse secretion and release ofgonadotropin-releasing hormone （GnRH） are increased due to early activation of the hypothalamic-pituitary-gonadal axis,resulting in developmental abnormalities with gonadal development and appearance of secondary sexual characteristics.The CPP without organic disease is known as idiopathic CPP （ICPP）.The objective of the study was to evaluate the clinical efficacy and safety of domestic leuprorelin （GnRH analog） in girls with ICPP.Methods：A total of 236 girls with ICPP diagnosed from April 2012 to January 2014 were selected and were randomized into two groups.One hundred fifty-seven girls in the test group were treated with domestic leuprorelin acetate,79 girls in the control group were treated with imported leuprorelin acetate.They all were treated and observed for 6 months.After 6-month treatment,the percentage of children with peak luteinizing hormone （LH） ≤3.3 U/L,the percentage of children with peak LH/peak follicle stimulating hormone （FSH） ratio 〈0.6,the improvements of secondary sexual characteristics,gonadal development and sex hormone levels,the change of growth rate of bone age （BA） and growth velocity,and drug adverse effects between two groups were compared.Results：After the treatment,the percentage of children with a suppressed LH response to GnRH,defined as a peak LH ≤3.3 U/L,at 6 months in test and control groups were 96.80% and 96.20%,respectively,and the percentage of children with peak LH/FSH ratio ≤0.6 at 6 months in test and control groups were 93.60% and 93.70%,respectively.The sizes of breast,uterus and ovary of children and the levels of estradiol （E2） were significantly reduced,and the growth rate of BA was also reduced.All the differences between pre-and post-treatment in each group were statistically significant （P 〈 0.05）,but the differences of the parameters between two groups were not significant （P 〉 0.05）.Conclusions：Domestic leuprorelin is effective and safe in the treatment of Chinese girls with ICPP.Its effectiveness and safety are comparable with imported leuprorelin.
