In vitro lipolysis process and lipolysis mechanism of testosterone undecanoate type Ⅲ lipid formulations / 药学学报

The study evaluates the lipolysis rate and extent of type Ⅲ lipid formulations using testosterone undecanoate as a model drug after digestion with in vitro lipolysis model, and studies the digestive regularity with optical microscope and electrical conductivity. The results showed that for testosterone undecanoate type Ⅲ lipid formulations with castor oil as oil phase and Transcutol HP as latent solvent, the lipolysis rate and extent were increased with the increase of oil phase proportion and were decreased with excessive proportion of surfactant, in which can see liquid crystal phase during lipolysis process. The lipolysis rate of type ⅢB lipid preparations with different surfactant were ordered as Labrasol > Tween 80 > Cremophor EL, but the rate of type ⅢA is different in quick digestion phase and slow digestion phase. The lipolysis extent of type Ⅲ lipid formulations with different surfactant were ordered as Cremophor EL > Tween 80 > Labrasol. These may be related to the digestive effect of pancreatic lipase on different surfactants. This study implied that the lipolysis rate and extent of type Ⅲ lipid formulations are greatly influenced by the proportion of oil phase and surfactant, and the surfactant structure. These factors will affect the in vivo digestion and should be taken into account when screening type Ⅲ lipid formulations.

Testosterone undecanoate supplementation together with human chorionic gonadotropin does not impair spermatogenesis in males with isolated hypogonadotropic hypogonadism: A retrospective study / 亚洲男科学杂志(英文版)

Gonadotropin therapy is commonly used to induce virilization and spermatogenesis in male isolated hypogonadotropic hypogonadism (IHH) patients. In clinical practice, 5.6%-15.0% of male IHH patients show poor responses to gonadotropin treatment; therefore, testosterone (T) supplementation can serve as an alternative therapy to normalize serum T levels and promote virilization. However, treatment with exogenous T impairs spermatogenesis and suppresses intratesticular T levels. This retrospective study aimed to determine whether oral testosterone undecanoate (TU) supplementation together with human chorionic gonadotropin (hCG) would negatively affect spermatogenesis in IHH patients compared with hCG alone. One hundred and seven IHH patients were included in our study. Fifty-four patients received intramuscular hCG and oral TU, and 53 patients received intramuscular hCG alone. The median follow-up time was 29 (range: 12-72) months in both groups. Compared with the hCG group, the hCG/TU group required a shorter median time to normalize serum T levels (P < 0.001) and achieve Tanner stage (III and V) of pubic hair and genital development (P < 0.05). However, there were no significant differences in the rate of seminal spermatozoa appearance, sperm concentration, or median time to achieve different sperm concentration thresholds between the groups. In addition, there were no significant differences in side effects, such as acne and gynecomastia, observed in both groups. This study indicates that oral TU supplementation together with hCG does not impair spermatogenesis in treated IHH patients compared with hCG alone, and it shortens the time to normalize serum T levels and promote virilization.

Testosterone undecanoate supplementation together with human chorionic gonadotropin does not impair spermatogenesis in males with isolated hypogonadotropic hypogonadism: a retrospective study / 亚洲男科学杂志(英文版)

Gonadotropin therapy is commonly used to induce virilization and spermatogenesis in male isolated hypogonadotropic hypogonadism (IHH) patients. In clinical practice, 5.6%-15.0% of male IHH patients show poor responses to gonadotropin treatment; therefore, testosterone (T) supplementation can serve as an alternative therapy to normalize serum T levels and promote virilization. However, treatment with exogenous T impairs spermatogenesis and suppresses intratesticular T levels. This retrospective study aimed to determine whether oral testosterone undecanoate (TU) supplementation together with human chorionic gonadotropin (hCG) would negatively affect spermatogenesis in IHH patients compared with hCG alone. One hundred and seven IHH patients were included in our study. Fifty-four patients received intramuscular hCG and oral TU, and 53 patients received intramuscular hCG alone. The median follow-up time was 29 (range: 12-72) months in both groups. Compared with the hCG group, the hCG/TU group required a shorter median time to normalize serum T levels (P < 0.001) and achieve Tanner stage (III and V) of pubic hair and genital development (P < 0.05). However, there were no significant differences in the rate of seminal spermatozoa appearance, sperm concentration, or median time to achieve different sperm concentration thresholds between the groups. In addition, there were no significant differences in side effects, such as acne and gynecomastia, observed in both groups. This study indicates that oral TU supplementation together with hCG does not impair spermatogenesis in treated IHH patients compared with hCG alone, and it shortens the time to normalize serum T levels and promote virilization.

Clinical study of eurycoma longifolia in treatment of erectile dysfunction in climacteric males / 重庆医学

Objective To investigate the effect and safety of eurycoma longifolia in the treatment of erectile dysfunction(ED) in climacteric males.Methods One hundred and thirty-four climacteric males with ED were divided into the observation group and control group,67 cases in each group.The observation group was given the therapy of eurycoma longifolia and the control group was treated with testosterone undecanoate.After 3-month treatment,the scores of EHS,SHIM,AMS,EDITS,changes of serum to-tal testosterone(TT),free testesterone(FT),luteinizing hormone(LH),follicle stimulating hormone(FSH)and sex hormone-bind-ing globulin(SHGB)and complication occurrence rate were compared between the two groups.Results After 3-month treatment, the scores of EHS,SHIM,AMS and EDITS,and serum TT and FT levels in the two groups were significantly improved(P<0.05),moreover the results in the observation group were better than those in the control group(P<0.05);serum LH and FSH in the observation group had no obvious changes compared with before treatment(P>0.05),while which in the control group were significantly decreased compared with before treatment(P<0.05);serum SHGB level in the observation group was decreased com-pared with before treatment(P<0.05),while which in the control group was increased compared with before treatment(P<0.05);the EDITS score in the observation group was higher than that in the control group(P<0.01);the complication incidence rate in the observation group was 2.29 %,which was significantly lower than 16.41% in the control group(P<0.05).Conclusion Eury-coma longifolia can significantly improve sexuality and sexual function in climacteric males.

Oral Testosterone Undecanoate Capsules combined with Qilin Pills for late-onset hypogonadism in males / 中华男科学杂志

Objective@#To investigate the clinical effects of oral Testosterone Undecanoate Capsules (TUC) combined with Qilin Pills (QLP) on late-onset hypogonadism (LOH) in men.@*METHODS@#Sixty-three LOH patients meeting the inclusion criteria were randomly divided into a control group (aged ［48.4 ± 6.2］ yr, n = 32) and an experimental group (aged ［47.2 ± 5.6］ yr, n = 31) to be treated with oral TUC (80 mg, qd) and TUC + QLP (6g, tid), respectively, both for 3 months. Comparisons were made between the two groups of patients in the IIEF-5 scores, total testosterone (TT) levels, and scores in the Aging Males' Symptoms (AMS) scale before and after treatment.@*RESULTS@#After treatment, the patients of the experimental group, as compared with the controls, showed a significantly increased IIEF-5 score (21.7 ± 5.8 vs 15.9 ± 4.7, P <0.05) and TT level (［16.7 ± 2.2］ vs ［13.1 ± 2.8］ nmol/L, P <0.05), but a decreased AMS score (20.7 ± 5.7 vs 31.3±6.5, P <0.05).@*CONCLUSIONS@#TUC combined with Qilin Pills has a better effect and a lower rate of adverse reactions than TUC used alone in the treatment of late-onset hypogonadism in males.

Dissolution detection of testosterone undecanoate capsule in vitro / 国际药学研究杂志

Objective To determin the dissolution of testosterone undecanoate capsule in vitro with an established HPLC method. Methods The dissolution was determined by the second method described in China(ChP) 2015, Pharmacopoeia. Totally 900 ml of 0.25% sodium lauryl sulfate solution with pH 6.8 phosphate buffer were used as dissolution media, and the rotation speed was 75 r/min. The dissolution time was 120 min and the dissolution was determined by HPLC. The HPLC column was phenomenex@ C18 column(250 mm×4.6 mm, 5µm). The mobile phase was 2-propanol-acetonitrile-water (45:45:10, V/V/V) with a flow rate of 1.0 ml/min and the detection wavelength of 240 nm. The column temperature was 40°C and the injection volume was 20 µl. Results The average recovery of the method was about 100.55% (n=9). The calibration curves showed good linearity(r2=0.9999, n=7) within ranges of 1- 50 µg/ml. Conclusion The method is convenient and sensitive in the dissolution determination of testosterone undecanoate capsule.

In vitro and in vivo Transdermal Penetration of Testosterone Undecanoate Binary Ethosomes Gel / 中国药师

Objective:To study the in vitro and in vivo transdermal penetration of testosterone undecanoate ( TU) binary ethosomes gel. Methods:TU binary ethosomes were prepared by an ethanol injection method, and using carbopol 941 as the gel base, TU binary ethosomes gel was prepared. Using mouse skin as the barrier, Franz cells were applied to explore the in vitro transdermal penetration of TU binary ethosomes and the gel. Rats were used as the animals, and TU binary ethosomes and the gel was respectively administrated on the back skin. At the predetermined time points, plasma samples were withdrawn to detect the concentration of TU, and the main pharmacokinetics parameters were calculated. Results: The in vitro transdermal penetration of TU binary ethosomes and the gel was both fitted first-order equation:Q=8. 68t+6. 78(r=0. 998 2) and Q=6. 09t+3. 09(r=0. 999 3), and the stable penetration rate was 8. 68 μg·cm-2 ·h-1 and 6. 09μg·cm-2 ·h-1 , respectively. After the 24-hour penetration, the residual amount in skin of TU binary ethosomes and the gel was (208. 80 ± 55. 26)μg·g-1 and (225. 60 ± 38. 90)μg·g-1 , respectively. The main pharmacokinet-ics parameters of TU binary ethosomes and the gel were Cmax of(18.50 ±2.75)mg·L-1 and(20.80 ±2.42)mg·L-1, tmax of(6.20 ± 0. 14)h and(9. 54 ± 0. 52)h, and AUC0-48h of(336. 74 ± 2. 05)h and(486. 30 ± 1. 68)h. Conclusion:TU binary ethosomes and the gel both exhibit promising in vitro transdermal penetration, and the gel shows better sustained release property.

Dissolution detection of testosterone undecanoate capsule in vitro / 国际药学研究杂志

Objective To determin the dissolution of testosterone undecanoate capsule in vitro with an established HPLC method. Methods The dissolution was determined by the second method described in China(ChP)2015,Pharmacopoeia. Totally 900 ml of 0.25%sodium lauryl sulfate solution with pH 6.8 phosphate buffer were used as dissolution media,and the rotation speed was 75 r/min. The dissolution time was 120 min and the dissolution was determined by HPLC. The HPLC column was phenomenex@C18 column(250 mm×4.6 mm,5μm). The mobile phase was 2-propanol-acetonitrile-water(45∶45∶10,V/V/V)with a flow rate of 1.0 ml/min and the detection wavelength of 240 nm. The column temperature was 40℃and the injection volume was 20μl. Results The average recovery of the method was about 100.55%(n=9). The calibration curves showed good linearity(r2=0.9999,n=7)within ranges of 1-50μg/ml. Conclusion The method is convenient and sensitive in the dissolution determination of testosterone undecanoate capsule.

Suppression of spermatogenesis by testosterone undecanoate-loaded injectable in situ-forming implants in adult male rats / 亚洲男科学杂志(英文版)

We have investigated the feasibility of administration of testosterone undecanoate (TU)-loaded injectable in situ-forming implant (ISFI) for contraception in adult male Sprague-Dawley rats. Male rats were treated with vehicle, TU-loaded ISFIs (540, 270 and 135 mg TU kg-1 ) or TU injections (45 mg TU kg-1 every 30 days) for 120 days. Fertility tests served for determining infertility or restoration of fertility in treated rats. Serum testosterone concentration, epididymal sperm count, motility, morphology, and histology of the testis were monitored. The TU-loaded ISFIs increased serum testosterone levels in rats steadily without fluctuation over 3 months. One month after TU administration, the epididymal sperm count decreased significantly in all experimental groups. After 3 months, the animals treated with 270 and 135 mg kg-1 TU-loaded ISFIs were 100% infertile, and no implantation sites were produced in the mated females. However, some of males treated with 540 mg kg-1 ISFI or TU injections were still fertile but numbers of implantation sites were also significantly lower than control values. TU-loaded ISFI at an appropriate dose has potential as a long-acting male contraceptive drug that suppresses spermatogenesis consistently over a period of 3 months.

Comparison of in vivo and in vitro Permeation Behaviors of the Ethosome Gels of Testosterone and Its Es-ters / 中国药房

OBJECTIVE:To compare in vivo and in vitro permeation behaviors of the ethosome gels of testosterone,testoster-one propionate and testosterone undecanoate. METHODS:The ethosome gels of testosterone,testosterone propionate and testoster-one undecanoate were prepared. With cumulative permeating amount and permeation rate as the indexes,Franz diffusion cell and HPLC were employed to compare in vitro permeation behaviors of 3 kinds of ethosome gels in mouse skin. With testosterone patch as the positive control drug, electrochemistry method was adopted to detect the concentration of testosterone in plasma 0,3,6, 9,12,24,36 and 48 h after applying such 3 kinds of ethosome gels on the back of rats,and then pharmacokinetic parameters were calculated with DAS 2.0 software. RESULTS:24 h cumulative permeating amounts of the ethosome gels of testosterone,tes-tosterone propionate and testosterone undecanoate were(234.31±13.8),(175.63±41.1)and(72.60±15.3)μg/cm2,and the per-meation rates were(10.25±1.9),(7.64±1.4)and(2.96±0.8)μg/(cm2·h),respectively. The pharmacokinetic parameters of the above-mentioned three kinds of ethosome gels and the positive control drug were respectively as follows as cmax of(20.19±2.57), (17.50±2.91),(0.23±0.04),(14.97±2.12)ng/ml,t1/2Ka of(2.80±0.45),(3.36±0.59),(4.02±0.62),(4.20±0.71)h,AUC0-48 h of(13.85±1.96),(13.93±2.13),(0.35±0.07),(11.76±2.31)ng·h/ml. CONCLUSIONS:in vivo and in vitro permeation behav-iors of the ethosome gels of testosterone and testosterone propionate are fairly good.

Formula Optimization and Quality Evaluation of Testosterone Undecanoate Binary Ethosomes / 中国药师

To screen the optimal formula and evaluate the quality of testosterone undecanoate ( TU) binary ethosomes to lay the foundation for the transdermal delivery system of TU. Methods:The mixture of ethanol and propylene glycol was used as the softeners, and TU binary ethosomes were prepared by ethanol injection method. The ratio of TU to lipids ( A) , the quality percentage of the mixture of ethanol and propylene glycol ( B) and the ratio of ethanol to propylene glycol ( C) as the influencing factors, and the entrapment efficiency as the index, an orthogonal test was used to optimize the formula of TU binary ethosomes. The morphology, size, zeta potential, in vitro drug release and stability of TU binary ethosomes were studied. Results:The optimal formula of TU binary etho-somes were as follows:the ratio of TU to lipids was 1∶15, the quality percentage of the mixture of ethanol and propylene glycol was 10% and the ratio of propylene glycol to ethanol was 6∶4. The optimal TU binary ethosomes were concentric circles under an optical microscope with uniform size, and the average size was (185. 5 ± 52. 8)nm, zeta potential was ( -15. 87 ± 0. 26)mV, and the entrap-ment efficiency was (79. 14 ± 0. 66)%. TU release from the binary ethosomes in vitro was fitted the first-order equation:Q=20. 79t-11. 01 (r2 =0. 998 4). Under the high temperature, the entrapment efficiency was decreased significantly, while under the other test conditions, all the indices of TU binary ethosomes showed no significant difference. Conclusion:The optimal TU binary ethosomes are easy to be prepared with promising quality and sustained release property in vitro, which are valuable to be studied further.

Effects of administering testosterone undecanoate in rats subjected to physical exercise: effects on the estrous cycle, motor behavior and morphology of the liver and kidney / Efeitos da administração de undecanoato de testosterona em ratos submetidos a exercício físico: efeitos sobre o ciclo estral, o comportamento motor e a morfologia do fígado e do rim

The aim of the work was evaluate the effects of testosterone undecanoate (TU) treatment combined with moderate physical training on: the estrous cycle, body weight (BW), motor behavior (MB), and the morphohistology of the reproductive system, the liver and kidney in rats. Female Wistar rats (180 g - 250 g) were divided as follows: sedentary + TU (S + TU), trained + TU (T + TU), sedentary + vehicle (S + V), trained + vehicle (T + V). The rats swam 50 min/Day, strapped with a 5 percent BW load, for 4 weeks. During this training, (BW) was monitored daily as well as the estrous cycle (EC) by vaginal smear. The TU (15 mg/kg s.c) was administered 3 times/week for 4 weeks. At the end of the study, data on MB, BW and morphohistopathological changes in viscera were compiled. The (T + TU) group had on average, a higher (BW) in the fourth week compared to the first week, and (BW) higher than (S + V) and (S + TU) groups. We noted an interruption in the EC and a decrease in weight of ovaries in animals treated with TU. In addition, there was an increase in the relative weight of the heart in groups (T + V) and (T+ TU), and kidneys in group (T + TU). Histopathological analysis showed periportal congestion and isolated foci of hepatic necrosis in rats with TU. Thus, TU combined with training abolished the EC, promoted ovarian atrophy, liver necrosis, cardiac hypertrophy and a decrease in motor activity.

O objetivo do trabalho foi avaliar o efeito do tratamento com undecanoato de testosterona (UT) combinado ao treinamento físico moderado sobre ciclo estral, peso corporal, estruturas do sistema reprodutor, comportamento motor e morfologia hepática e renal em ratas. Ratas Wistar (180 a 250 g) foram divididas em: sedentárias + UT (S+UT), treinadas + UT (T+UT), sedentárias + veículo (S+V), treinadas + veículo (T+V). As ratas nadaram 50 min/dia com sobrecarga de ~5 por cento do peso corporal por 4 semanas. Durante o período de treinamento foi realizado acompanhamento diário do peso corporal (PC) e do ciclo estral (CE) pelo esfregaço vaginal. O UT (15 mg/kg s.c.) foi administrado 3x/semana durante 4 semanas. Ao final foram avaliados comportamento motor, pesos e alterações histopatológicas de alguns órgãos. O grupo T+UT apresentou PC maior na quarta semana do que na primeira, com pesos corporais maiores que os grupos S+V e S+UT. Houve interrupção no CE e redução do peso dos ovários nos animais tratados com UT. Houve aumento do peso relativo do coração, nos grupos T+V e T+UT, e do peso relativo dos rins, no grupo T+UT. A análise histopatológica revelou congestão periportal e focos isolados de necrose hepática nas ratas com UT. O UT combinado com treinamento produziu supressão do ciclo estral, atrofia ovariana, necrose hepática, hipertrofia cardíaca e redução da atividade motora.

Oral Testosterone Undecanoate Versus Transdermal Testosterone Gel for the Treatment of Testosterone Deficiency Syndrome: A Retrospective Comparative Study / 대한남성과학회지

PURPOSE: Oral testosterone undecanoate and transdermal testosterone gel are the testosterone formulas widely prescribed as hormonal replacement for tesosterone deficiency syndrome (TDS) in male patients. We evaluated the changes in serum testosterone level and the effects of these medicines. MATERIALS AND METHODS: The medical records of 162 patients who were diagnosed with TDS based on serum testosterone (0.05). The initial and final testosterone levels of the two groups were not significantly different. However, the peak level during treatment was significantly higher in group II (p<0.05). The maximal increment of testosterone level was also significantly higher in group II. Initially, group II reached its peak testosterone level earlier than group I. The final serum levels were not significantly different after adjustment of dosages in group I. Testosterone replacement significantly decreased the AMS scales in both groups. CONCLUSIONS: Both oral testosterone undecanoate and transdermal testosterone gel improved the serum testosterone level and symptom score for those with TDS. Transdermal testosterone gel may reach the peak serum testosterone level faster than oral testosterone undecanoate. Large prospective studies are required to assess the precise role of testosterone replacement therapy.

Oral Testosterone Undecanoate(Andriol(R)) for Increasing Serum Testosterone Level in Late Onset Hypogonadism Patients / 대한남성과학회지

PURPOSE: Testosterone undecanoate(Andriol(R)) has been widely prescribed for late onset hypogonadism. But we believe that the major limitation of Andriol is not ineffectiveness butmay be limited by poor bioavailability. We retrospectively evaluated the changes of in serum testosterone levels correlation ofin relation to daily dose and time to taking medicineof day at which the medicine is taken, retrospectively. MATERIALS AND METHODS: We reviewed 135 medical records of late onset hypogonadism patients who have had been prescribed testosterone undecanoate. Statistical analysis was done to identify the any correlations of between dosage, medication timing(after meals or during meals), age, serum testosterone level(initial, peak during therapy, final), and duration of therapy. RESULTS: Mean age, duration of therapy and daily dosage was were 50.1+/-14.2 years, 311+/-283 days, and 3.5+/-1.3 tablets, respectively. Initial, final, and peak serum testosterone levels(ng/dl) was were 1.9+/-1.1, 2.7+/-1.7, and 3.4+/-1.8, respectively. The peak and final testosterone levels were highly correlated(r=0.80) and significantly elevated compared to the initial level(p<0.01, both). Patients taking medicine during the meals showed a significantly higher increment of peak testosterone level compared to those taking it after meals(p=0.04). The serum testosterone level was positively correlated to dosage until up to 4 tablets per day, but not after at 5 tablets or more. Initial serum testosterone level was negatively correlated to the final increment of testosterone level. Duration of therapy and, age of patient was were not correlated to final increment of testosterone level. CONCLUSIONS: In this study, oral testosterone undecanoate effectively elevated serum testosterone level. And it was more effective for the patients of having lower initial serum testosterone. These results suggest that an optimal prescription of oral testosterone undecanoate can effectively increase the serum concentration of testosterone. For a more conclusive of findings on the effectiveness of oral testosterone undecanoate, large prospective studies are will be required.

Oral Testosterone Undecanoate(Andriol(R)) for Increasing Serum Testosterone Level in Late Onset Hypogonadism Patients / 대한남성과학회지

PURPOSE: Testosterone undecanoate(Andriol(R)) has been widely prescribed for late onset hypogonadism. But we believe that the major limitation of Andriol is not ineffectiveness butmay be limited by poor bioavailability. We retrospectively evaluated the changes of in serum testosterone levels correlation ofin relation to daily dose and time to taking medicineof day at which the medicine is taken, retrospectively. MATERIALS AND METHODS: We reviewed 135 medical records of late onset hypogonadism patients who have had been prescribed testosterone undecanoate. Statistical analysis was done to identify the any correlations of between dosage, medication timing(after meals or during meals), age, serum testosterone level(initial, peak during therapy, final), and duration of therapy. RESULTS: Mean age, duration of therapy and daily dosage was were 50.1+/-14.2 years, 311+/-283 days, and 3.5+/-1.3 tablets, respectively. Initial, final, and peak serum testosterone levels(ng/dl) was were 1.9+/-1.1, 2.7+/-1.7, and 3.4+/-1.8, respectively. The peak and final testosterone levels were highly correlated(r=0.80) and significantly elevated compared to the initial level(p<0.01, both). Patients taking medicine during the meals showed a significantly higher increment of peak testosterone level compared to those taking it after meals(p=0.04). The serum testosterone level was positively correlated to dosage until up to 4 tablets per day, but not after at 5 tablets or more. Initial serum testosterone level was negatively correlated to the final increment of testosterone level. Duration of therapy and, age of patient was were not correlated to final increment of testosterone level. CONCLUSIONS: In this study, oral testosterone undecanoate effectively elevated serum testosterone level. And it was more effective for the patients of having lower initial serum testosterone. These results suggest that an optimal prescription of oral testosterone undecanoate can effectively increase the serum concentration of testosterone. For a more conclusive of findings on the effectiveness of oral testosterone undecanoate, large prospective studies are will be required.

Improving height velocity in boys with constitutional delayed growth and puberty (CDGP) by using oral testosterone undecanoate.

Treatment with oral testosterone undecanoate (40 mg daily) in 9 boys diagnosed as having constitutional delayed growth and puberty (CDGP) was studied. The mean chronological age was 12.1+ 1.7 years and the mean duration of treatment was 0.7+ 0.3 year. The height velocity was increased from 3.9+ 2.1 cm per year before treatment up to 8.1+ 2.3 cm per year treatment (p=0.003). However, the predicted adult height was not different between pre and post treatment. Eighty-nine percent of children reached the pubertal testicular size after treatment. Therefore, oral testosterone undecanoate was proved to be effective to improve height velocity but the predicted adult height in CDGP boys.