Chinese Female Volunteers Research Articles

Establishing the Inhibition of the Serine Protease Plasmin as a Skin Anti-Aging Pathway

Plasmin is a serine protease induced by UV-irradiation in skin that contributes to inflammation. We showed that plasmin is upregulated in photo-exposed facial skin and that this correlates with increased transepidermal water loss (TEWL). Plasmin activity upregulates downstream pathways such as pro-inflammatory cytokines and matrix-metalloproteinases (MMPs). In addition, the plasminogen system modulates cutaneous melanogenesis. In this study, we investigated potential skin-aging effects of plasmin with a dual inhibitor of plasmin and its activator urokinase (uPA). We established a range of in vitro and ex vivo assays to investigate inflammation, MMP-9 activation, and collagen modulation, and the melanogenesis modulation activity of plasmin. A specific plasmin inhibitor, Amidinobenzyl Benzylsulfonyl D-Seryl Homophenylalaninamide Acetate (ABSHA), was used in these assays to downregulate these effects. We found that ABSHA was able to down-regulate UV-irradiation-induced MMP-9 expression, and subsequent collagen IV degradation, ex vivo. In addition, the increased melanin synthesis in epidermal melanocytes was reduced significantly by ABSHA. Furthermore, dermal fibroblasts treated with the plasmin inhibitor showed increased collagen I synthesis. We further investigated these effects in a two-month, monocentric, placebo-controlled human study on female Chinese volunteers. We found a significant increase in collagen density by ultrasound measurement and an increase in elasticity by cutometer assessment in the group using a formulation consisting of a 10 ppm ABSHA solution. This resulted in decreased wrinkle volumes on both the forehead and crow’s feet as shown by Primos CR. Looking at age spots, there was a decrease in overall ITA° and melanin density as well as in the total age spot area. Our results establish plasmin as a skin-aging enzyme. Using specific inhibitors against plasmin shows promise against age-induced skin conditions.

Facial Skin Aging Characteristics of the Old-Perceived Age in a 20-40 Years Old Chinese Female Population.

In the quest for a youthful appearance, women use a variety of anti- aging cosmetics. Defining skin problems is especially important for the selection of anti-aging solutions. However, the skin problems faced by Chinese women at different ages are different. This study aimed at Chinese women aged 20-40 years old and analyzed facial skin aging characteristics of those with old-perceived age. The total of 400 standard facial photographs from Chinese female volunteers aged 20-40 was assessed by another 126 Chinese women. The facial areas and skin aging characteristics that influenced age estimation were collected at the same time. Skin aging characteristics, including wrinkles, skin tone, pigmentation and pores, were analyzed based on facial photographs. Groupings were made based on deviation of perceived age from chronological age, and skin aging characteristics among groups were compared. The perceived age of Chinese women aged 20-40 has a moderate correlation with chronological age. Women aged 20-30 generally had an old-perceived age. Deep skin tone was a prominent problem in this age group, with those who had the older-perceived age observed the darker and redder skin tone. Women aged 31-40 were perceived partly old but appeared with wrinkle aggravation, as well as deepening of redness, enlarged pores, and increased pigmentation at the mid-face. The perceived older women also had more visible frown lines and darker skin tone at the upper face. The perceived age of Chinese women aged 20-40 tends to deviate from their chronological age. Women aged 20-30 with old-perceived age are associated with deep skin tone, even found darker and redder in older-perceived women group, while women aged 31-40 are associated with wrinkles and deterioration at mid-face area and upper-face problems drive more attention in older-perceived women group.

Safety and Pharmacokinetics of PSD502 in Healthy Chinese Male and Female Volunteers: Two Randomized, Double-Blind, Placebo-Controlled, Phase I Trials.

PSD502 is a metered-dose spray for premature ejaculation. The two trials aimed to evaluate the safety and pharmacokinetics of PSD502 in healthy Chinese male and female individuals. Two phase I, randomized, double-blind, placebo-controlled trials were conducted in men (Trial 1) and women (Trial 2). The participants were randomized 3:1 to receive PSD502 (7.5 mg of lidocaine and 2.5 mg of prilocaine per spray) or a placebo. For male individuals, a single dose (three sprays) once daily was applied to the glans penis for 21 days except for nine sprays (three doses) on days 7 and 14, 4 h apart for each dose. For female individuals, two sprays were applied to the vagina and one to the cervix once daily for 7 days. The primary endpoint was safety. Pharmacokinetics analysis was also performed. Twenty-four male and 24 female individuals were recruited. Treatment-emergent adverse events occurred in 38.9% (7/18) of male individuals and 66.7% (12/18) of female individuals in the PSD502 group, respectively. Both trials reported 50.0% (3/6) treatment-emergent adverse events for the placebo. No grade ≥ 3 treatment-emergent adverse events, serious adverse events, or treatment-emergent adverse events leading to early withdrawal or discontinuation occurred. After consecutive applications, lidocaine and prilocaine cleared rapidly in both trials. Plasma concentrations exhibited high inter-individual variability. The maximum plasma concentrations of active ingredients were far below the anticipated minimum toxic concentrations. The area under the plasma concentration-time curve of metabolites were ≤ 20% of the parent drugs. No clinically significant accumulations were observed in the two trials. PSD502 was well tolerated and showed low plasma concentrations in healthy Chinese male and female individuals.

Pharmacokinetics, Bioequivalence, and Safety Evaluation of Dienogest in Healthy Subjects Under Fasting and Fed Conditions.

Dienogest is effective in reducing endometriosis-related pain symptoms. This study aims to investigate and compare the pharmacokinetic profiles and safety of test formulations to reference formulations of dienogest in healthy Chinese female volunteers under fasting or fed conditions. The purpose of this single-center, randomized, open-label, 2-sequence, 2-period crossover clinical trial was to evaluate the safety and pharmacokinetic profiles of the 2 formulations under fasting and fed conditions. Additionally, 48 healthy female volunteers were selected and divided at random into the fasting and the fed group. After dosing, the venous blood was collected through indwelling catheters. Dienogest plasma concentrations were measured using liquid chromatography-tandem mass spectrometry after the plasma samples were prepared with the protein precipitation method. Under either fasting or fed conditions, the pharmacokinetic parameters (maximum observed concentration, area under the concentration-time curve [AUC] from time 0 to the last measurable concentration, and AUC from time 0 to infinity) for dienogest between the test and reference products, geometric mean ratio, and 90%CI were all within the range of 80%-125%. The 2 dienogest products were bioequivalent. Based on maximum observed concentration and AUC from time 0 to the last measurable concentration, the generic dienogest was bioequivalent to the original dienogest in this study conducted under fasting and fed conditions in healthy Chinese women (study CTR20190063 on chinadrugtrials.org.cn registry).

How to Achieve Sufficient Endogenous Insulin Suppression in Euglycemic Clamps Assessing the Pharmacokinetics and Pharmacodynamics of Long-Acting Insulin Preparations Employing Healthy Volunteers.

The therapeutic effect of basal insulin analogs will be sustained at a rather low insulin level. When employing healthy volunteers to assess the pharmacokinetics (PK) and pharmacodynamics (PD) of long-acting insulin preparations by euglycemic clamp techniques, endogenous insulin cannot be ignored and sufficient endogenous insulin inhibition is crucial for the PD and/or PK assessment. This study aimed to explore a way to sufficiently inhibit endogenous insulin secretion. Healthy Chinese male and female volunteers were enrolled. After a subcutaneous injection of insulin glargine (IGlar) (LY2963016 or Lantus) (0.5 IU/kg), they underwent a manual euglycemic clamp for up to 24 h where the target blood glucose (BG) was set as 0.28 mmol/L below the individual’s baseline. Blood samples were collected for analysis of PK/PD and C-peptide. The subjects fell into two groups according to the reduction extent of postdose C-peptide from baseline. After matching for the dosage proportion of Lantus, there were 52 subjects in group A (C-peptide reduction<50%) and 26 in group B (C-peptide reduction≥50%), respectively. No significant difference was detected in age, body mass index, the proportion of Latus treatment and female participants. A lower basal BG was observed in group B compared to group A (4.35 ± 0.26 vs. 4.59 ± 0.22 mmol/L, p < 0.05). The clamp studies were all conducted with high quality (where BG was consistently maintained around the target and exhibited a low variety). The binary logistic regression analysis indicated low basal BG as an independent factor for the success of sufficient endogenous insulin suppression. In conclusion, setting a lower sub-baseline target BG (e.g., 10% instead of 5% below baseline) might be an approach to help achieve sufficient endogenous insulin suppression in euglycemic clamps with higher basal BG levels (e.g., beyond 4.60 mmol/L).

Pharmacokinetics and safety evaluation of oral Palonosetron in Chinese healthy volunteers: A phase 1, open-label, randomized, cross-over study

PurposePalonosetron hydrochloride is a specific 5-HT3 receptor antagonist, used to prevent chemotherapy-induced nausea and vomiting (CINV), and is a known chemical entity currently registered in the oral and IV forms in several countries worldwide. MethodsSingle-center, single-dose, 3-treatment, open-label, randomized, 3-period, phase-I cross-over study, conducted in 18 individuals (16 males and 2 females). The primary objective was to assess the pharmacokinetic profile of Palonosetron 0.25, 0.5 and 0.75mg, after a single, oral administration in Chinese male and female healthy volunteers. ResultsAfter administration of a single oral dose of 0.25mg, 0.5mg, or 0.75mg palonosetron in Chinese male and female healthy subjects, plasma palonosetron concentrations reached maximum values (Cmax) of 673 ± 151 pg/mL, 1330 ± 258 pg/mL, and 1990 ± 490 pg/mL, respectively, at 3-5 h (tmax). The plasma elimination half-life for 0.25, 0.5 and 0.75 mg of palonosetron was 41.8±9.72 hours, 44.6±8.59 hours and 42.3±8.51 hours, respectively. Single oral doses of 0.25mg, 0.5mg, or 0.75mg palonosetron were safe and well tolerated among all the 18 subjects involved. ConclusionsThe PK of palonosetron was found to be linear in the dose range of 0.25 to 0.75 mg. Oral palonosetron in doses up to 0.75 mg was well tolerated in healthy Chinese subjects. The PK and safety data obtained from this study were similar to previous phase I studies with IV palonosetron.

Tetrabromobisphenol A induces THR β-mediated inflammation and uterine injury in mice at environmentally relevant exposure concentrations

Tetrabromobisphenol A (TBBPA) is a widely used flame retardant, but the adverse outcomes induced by TBBPA has not been fully elucidated. In this study, TBBPA was detected in 54.9% of 102 female Chinese volunteers with an average serum concentration of 0.34 ng/mL. To investigate whether TBBPA induces adverse outcomes at environmentally relevant exposure doses, the mice were exposed to TBBPA for 14 and 28 days. The internal doses of TBBPA in mice serum were nearly the internal doses in volunteers. TBBPA significantly increased the secretion of some pro-inflammatory cytokines and suppressed immune responses in mice under such serum concentrations after 14- and 28-days exposure. Interestingly, uterine edema was observed in TBBPA-treated mice. In primary uterine cells model, the results showed TBBPA exposure suppressed THRβ expression, leading to the activation of the inflammatory PI3K/NF-κB signaling pathway. Our findings indicated that the uterus is the susceptible target organ of TBBPA and TBBPA exposure might increase risk of uterine cancer through deregulating inflammation pathways.

Perceived age and perceived health among a Chinese cohort: Does it mean the same thing?

Previous investigations have aimed at investigating parameters affecting age perception on several ethnicities. Perceived health has been a newer focus on Caucasian skin, yet little is known on the skin features used to estimate the health status of Chinese women and we aimed to investigate whether these cues are the same as those used for age perception. Age and health appearance of 276 Chinese female volunteers were estimated from their photographs by 1025 female naïve Chinese graders 20-69years old. Models were built to predict perceived age and health from topographic, colour and biophysical measured variables, in two subsets of the studied volunteers: below and above 50years. Machine learning-based predictive models for age and health perception were built on the collected data, and the interpretability of the models was established by measuring feature importance. Age perception was mostly driven by topographic features, particularly eye bags and eyelid sagging in the group below 50years old. Wrinkles, notably from the lower part of the face and oval of the lower face, were found to be more relevant in the group above 50years. Health appearance was primarily signalled by skin imperfections and global pigmentation in the subset below 50years, whereas colour-related parameters and skin hydration acted as health cues for the subset above 50years. Distinct skin features were acting as cues for age perception and/or health perception and varied per age subset. Their contribution should be borne in mind when designing products for 'younger looking skin' and 'healthier looking skin'.

Quantitative evaluation of rejuvenation treatment of nasolabial fold wrinkles by regression model and 3D photography.

With the application of 3D photography, our study aimed to quantify parameters of static nasolabial fold wrinkles and establish mathematic regression model between parameters of wrinkles and age, further to quantitatively evaluate the effect of rejuvenation treatment in terms of age. From October 2016 to May 2018, 433 Chinese female volunteers, aged 25-60years old, were enrolled in this study. Antera 3D camera was used to collect four parameters of static nasolabial fold wrinkles on the left and right sides of the volunteers, including overall size, average depth (mm), average width (mm), and maximum depth (mm). For those presented a linear relationship with age, univariate linear regression fitting was performed, followed by residual analysis, goodness of fit test, and significance test. The results of univariate linear regression fitting showed there was a clear linear relationship between the maximum depth, average depth, overall size of nasolabial fold wrinkles and age, and the regression equations were established. The significance test of regression coefficients showed P values were less than .0001. With application of the regression model between parameters of nasolabial fold wrinkles and age, the effect of rejuvenation treatment can be quantitatively evaluated in terms of age, which has certain reference and promotion value.

Ageing profiles of Caucasian and Chinese cohorts - focus on hands skin.

In spite of hand care being a dynamic segment of skin care, hands skin physiology has been receiving little attention in comparison to facial skin. In the present study, we aimed at gathering a comprehensive set of skin data from the dorsal part of the hand to study age related-changes in two ethnic groups (Caucasian and Chinese). Skin topographic, skin colour/colour heterogeneities, skin chromophores and skin biophysical measurements of 116 Caucasian and Chinese female volunteers aged 30-65years old were collected in Ireland and in China as part of a cross-sectional study. Topographic alterations happened at both micro and macro scales with a noticeable delay in the onset of 10years for the Chinese cohort. Similar evolution of skin colour with ageing was observed between the two cohorts and strong dissimilarities were seen when it came to colour heterogeneities and melanin hyper concentration, with a 20-year delay in severity for the Chinese cohort. A similar sharp drop of skin hydration occurred when reaching the 60's regardless of the group and substantial differences were recorded for skin biomechanical properties of the skin. These results provide additional insights about hand skin physiology in relation to ageing and ethnic differences, especially when put into perspective with what is currently known about facial ageing. This research yield additional material for hand cream product rationale and strategies for mitigating the appearance of ageing hands.

Instrumental Evaluation of the Depigmenting Efficacy of an Oral Supplementation Containing Peptides and Chrysanthemum Extract for the Treatment of Melasma

The aim of this study was to assess the efficacy of an oral supplement (CP) containing collagen peptide, soy peptide, and chrysanthemum extract in Chinese female adult volunteers with melasma. The approval of the Institutional Ethics Committee of the third affiliated hospital, Sun-Yat Sen University, was obtained before the study. A signed consent was obtained from each volunteer prior to study to enable the volunteer to appreciate the aim of the study and the consequences of her consent. Sixty-two female volunteers aged 30–60 years were included in the study, and were randomized into a treatment group or a placebo group. The skin tone of the pigmented spots was evaluated using Chromameter, and pigment density was evaluated using Mexameter before and after the treatment. Significant changes in skin tone parameters of L value and ITA° (individual typology angle) were detected in the lesion area after the treatment (P &lt; 0.01). When compared with placebo group, the treatment group achieved significant improvement in the brightness of the pigmented spots at the 45 and 60-day time points. A significant decrease in the level of melanin was observed in the treatment group when compared with the placebo group (p &lt; 0.01). All data demonstrated through non-invasive in vivo instrumental measurement that daily oral intake of CP had clinical efficacy of reducing melasma severity.

Pharmacokinetics and bioequivalence analysis of amlodipine tablets in Chinese female and male volunteers by HPLC-MS/MS

Pharmacokinetics and bioequivalence analysis of amlodipine tablets in Chinese female and male volunteers by HPLC-MS/MS

Pharmacokinetics of dimemorfan phosphate tablets in healthy Chinese volunteers.

Investigate the pharmacokinetic properties of the antitussive dimemorfan phosphate tablets in healthy male and female Chinese volunteers after single and multiple-dose administration; and to evaluate the food-effect on pharmacokinetics of dimemorfan. 12 subjects received a single dose of 10mg and 40mg dimemorfan phosphate tablets, respectively in study stage 1. Another 12 subjects received a single dose of 20mg dimemorfan phosphate tablets under fed conditions, a single dose of 20mg dimemorfan phosphate tablets under fasting conditions and multiple-dosing of 20mg dimemorfan phosphate tablets 3 times per day, respectively in study stage 2. The washout between each treatment was 1week. Plasma dimemorfan was quantified by a high pressure liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) method. After single-dosing of 10mg, 20mg and 40mg dimemorfan phosphate tablets, Cmax, AUC0-t and AUC0-∞ were dose proportional, which achievd 6.19±7.61ng·mL-1, 101±171 and 117±210ng·mL-1·h, respectively after single-dosing of 40mg dimemorfan phosphate tablets. Tmax ranged from 2.75 to 3.96h and t1/2 ranged from 10.6 to 11.4h. After multiple-dosing of 20mg dimemorfan phosphate tablets, the Accumulation Index (AI) was 2.65±1.11. The pharmacokinetic parameters after single-dosing of 20mg dimemorfan phosphate tablets under fed conditions were similar with those under fasting conditions. Sex did not affect the pharmacokinetics of dimemorfan phosphate tablets. Single-dosing of dimemorfan phosphate tablets exhibited linear kinetic characteristics. Multiple-dosing of 20mg dimemorfan phosphate tablets 3 times per day caused obvious accumulation. No food effect or sex effect on the pharmacokinetics of dimemorfan phosphate tablets was observed. Chictr.org identifier: ChiCTR-ONC-14004851.

Simultaneous determination of levonorgestrel and two endogenous sex hormones in human plasma based on LC-MS/MS.

Levonorgestrel (LNG) is a commonly used emergency contraceptive which can effect sex hormone levels in female blood. The objective of this study was to develop and validate a specific and sensitive LC-MS/MS method for monitoring endogenous sex hormone levels (17β-estradiol and progesterone) in female plasma after administration of LNG. Results & methodology: The method was developed, optimized and validated according to the EMA guideline. Assay validation met all the criteria, including good linearity in the range of 0.1-20 ng/ml for 17β-estradiol, as well as 0.2-30 ng/ml for LNG and progesterone. The method has been preliminarily applied to explore the variation trend of sex hormone levels in healthy Chinese female volunteers' plasma after oral administration of 1.5 mg LNG tablet. With LNG absorption into plasma, progesterone and estradiol levels descended rapidly, and maintained at low levels in the onset time.

Comparison of ESI– and APCI–LC–MS/MS methods: A case study of levonorgestrel in human plasma

Electrospray ionization (ESI) and atmospheric pressure chemical ionization (APCI) techniques for liquid chromatography–tandem mass spectrometry (LC–MS/MS) determination of levonorgestrel were evaluated. In consideration of difference in ionization mechanism, the two ionization sources were compared in terms of LC conditions, MS parameters and performance of method. The sensitivity for detection of levonorgestrel with ESI was 0.25ng/mL which was lower than 1ng/mL with APCI. Matrix effects were evaluated for levonorgestrel and canrenone (internal standard, IS) in human plasma, and the results showed that APCI source appeared to be slightly less liable to matrix effect than ESI source. With an overall consideration, ESI was chosen as a better ionization technique for rapid and sensitive quantification of levonorgestrel. The optimized LC–ESI–MS/MS method was validated for a linear range of 0.25–50ng/mL with a correlation coefficient ≥0.99. The intra- and inter-batch precision and accuracy were within 11.72% and 6.58%, respectively. The application of this method was demonstrated by a bioequivalence study following a single oral administration of 1.5mg levonorgestrel tablets in 21 Chinese healthy female volunteers.

Pharmacokinetics of simvastatin lactone and its active metabolite simvastatin hydroxy acid in healthy Chinese male and female volunteers

Gender differences in pharmacokinetics have been reported to have important clinical consequences; however, no information about differences in the pharmacokinetics of the cholesterol-lowering drug simvastatin lactone and its metabolite, simvastatin hydroxy acid, in males and females is available. The aim of this study was to investigate the effect of gender on the pharmacokinetics of simvastatin lactone and simvastatin hydroxy acid in healthy Han Chinese volunteers. 16 healthy volunteers (8 males and 8 females) were orally administered a single dose of 40 mg simvastatin lactone after an overnight fast. Plasma was then collected 24 hours after simvastatin lactone administration. Concentrations of simvastatin lactone and simvastatin hydroxy acid were measured by high performance liquid chromatography/mass spectrometry/mass spectrometry (HPLC/MS/MS). There were no significant associations between the pharmacokinetic parameters of simvastatin lactone and gender. For simvastatin hydroxy acid, peak plasma concentrations (Cmax) and dose-normalized by the subject weight Cmax (NCmax) were higher in females than in males. Furthermore, NCmax and dose-normalized by the subject weight AUC (NAUC0-24h, NAUC0-∞) ratios of simvastatin hydroxy acid to simvastatin lactone in females were higher than in males. This study indicates that gender affects the plasma concentrations of active simvastatin hydroxy acid, but has no significant effect on parent simvastatin lactone. Raised plasma concentrations of simvastatin hydroxy acid in females may enhance the risk of systemic adverse effects during simvastatin lactone treatment.

Correlation of Circulating Matrix Metalloproteinase-3 and Osteopontin Levels with Postmenopausal Osteoporosis

Objective: To study Matrix Metalloproteinase-3 (MMP-3) and Osteopontin (OPN) levels and correlations of MMP- 3 and OPN with Bone Metabolic Markers and Bone Mineral Density (BMD) in postmenopausal Chinese women. Methods: MMP-3, OPN Osteoprotegrin (OPG), Osteoprotegrin Ligand (OPGL) of 120 postmenopausal Chinese female volunteers was measured using ELISA. BMD were measured using dual energy X-ray absorptiometry. According to the criteria of WHO, women were divided into 3 groups, such as normal, oteopenia and osteoporosis group. Results: OPN concentrations were significantly higher in osteoporosis (56 ± 20) ng/ml than normal (26 ± 11) ng/ml (P<0.05). But MMP-3 concentrations were little higher in osteoporosis (153 ± 121) ng/ml than normal (125 ± 101) ng/ml. In osteoporosis, notable negative correlations between OPN, ratio of OPN/MMP-3 and BMD, sOPGL were found (P<0.05) as well as positive relations between OPN, ratio of OPN/MMP-3 and sOPG (P<0.05), and positive relation of MMP-3 and BMD of Ward’s triangle was existed (P<0.05), in osteopenia negative relations of MMP-3 and BMD as well as ratio of OPN/MMP-3 were detected (P<0.05). Conclusion: There are significant correlations between serum OPN, ratios of OPN and MMP-3 and bone biomarkers of sOPG, sOPGL, OPN and OPN/MMP-3 may increase with high bone-metabolism. The increases of OPN and ratio of OPN/MMP-3 appear possibly as a concomitant event in high bone turnover state, such as postmenopausal osteoporosis.

Bioequivalence of Two Misoprostol Tablets in Healthy Chinese Female Volunteers: A Single-Dose, Two-Period, Double Crossover Study

To assess the bioequivalence of a new generic formulation of misoprostol (CAS 59122-46-2) 0.2 mg tablets (test) and the available branded tablet (reference) for the requirement of state regulatory criteria and the marketing of the test product in China. A randomized-sequence, 2-period crossover study was conducted in 20 healthy Chinese female volunteers in the fasted state. Blood samples were collected at baseline and 0.083, 0.17, 0.25, 0.33, 0.5, 0.75, 1, 1.25, 1.5, 2, 3, 4 and 6 h after a single oral dose of 0.6 mg misoprostol test or reference, followed by a 7-day washout period. Misoprostol acid, the active metabolite of misoprostol, was determined by an HPLC-MS/MS method. Drug And Statistics 2.0 was used to calculate the pharmacokinetics parameters and assess bioequivalence of the 2 formulations. It was considered bioequivalent if the 90% CIs of the mean ratios (test: reference) for Tmax, Cmax and AUC0-t were all within the range from 80% to 125%. Adverse events were monitored throughout the study based on clinical parameters and patient reports. The main pharmacokinetics parameters for the test and reference were as follows: t1/2 was (0.680 ± 0.371) h and (0.650 ± 0.264) h; Tmax was (0.415 ± 0.087) h and (0.399 ± 0.097) h; Cmax was (1.941 ± 0.417) ng/mL and (2.047 ± 0.397) ng/mL; AUC0-t was (1.535 ± 0.419) ng·h/mL and (1.652 ± 0.400)ng·h/mL, and the AUC0-∞ was (1.576 ± 0.465) ng·h/mL and (1.686 ± 0.396) ng·h/mL. The mean ratios (test: reference) for Cmax, AUC0-t, and AUC0-∞ were 95.3% ±13.2%, 92.65% ± 17.31%, and 93.61%±18.97%, respectively. No significant (p>0.05) differences in pharmacokinetic parameters were found between preparations, treatments and periods. This single-dose study in healthy Chinese fasted volunteers was shown that the misoprostol test and reference met the requirement of US and China regulatory criterion, and the test and reference were bioequivalent.

Genistein alters caffeine exposure in healthy female volunteers

This study investigated the effect of 1 g genistein daily for 14 days on caffeine-based metrics of cytochrome P4501A2 (CYP1A2), cytochrome P4502A6 (CYP2A6), N-acetyltransferase 2 (NAT2), and xanthine oxidase (XO). A single dose of 100 mg caffeine was administered once before and once on the last day of a 14-day treatment regime with 1 g genistein once daily to 18 healthy female volunteers. Urine and blood samples were collected up to 12 and 24 h, respectively, after each caffeine dose. Using high-performance liquid chromatography (HPLC), caffeine and 1,7-dimethylxanthine (17X) were quantified in plasma, whereas 17X, 1,7-dimethylurate (17U), 1-methylxanthine (1X), 1-methylurate (1U), and 5-acetylamino-6-formylamine-3-methyluracil (AFMU) were quantified in urine. Urinary metabolite ratios were calculated to assess enzyme activities and compared between administrations using analysis of variance (ANOVA). Genistein decreased the urinary caffeine metabolite ratio used to assess CYP1A2 activity by 41% [90% confidence interval (CI) 28-51%). The urinary ratio indicating XO activity decreased by 29% (90% CI 24-32%), whereas urinary ratio for CYP2A6 activity increased by 47% (90% CI 29-66%) after 2 weeks of genistein. The NAT2 urinary caffeine metabolite ratio did not change significantly. Two weeks of intake of 1 g genistein daily led to decreases in CYP1A2 and XO activity and an increase in CYP2A6 activity, whereas NAT2 activity did not change in healthy Chinese female volunteers. Pharmacokinetics of other substrates of the enzymes investigated here may be influenced in a similar manner.

Effect of Soy Extract Administration on Losartan Pharmacokinetics in Healthy Female Volunteers

osartan is metabolized by CYP2C9 and CYP3A4 to an active metabolite, E-3174, which has greater antihypertensive activity than the parent compound. Soy extract has been shown to be an activator of CYP2C9 and CYP3A4 in vitro. Coadministration of soy extract and losartan may therefore alter the pharmacokinetics of losartan and E-3174. To determine whether, when losartan was used in combination with soy extract, a significant pharmacokinetic interaction would be observed in healthy female volunteers. Eighteen healthy Chinese female volunteers were recruited. In an open-label, 2-phase study, losartan 50 mg was given to each subject, with and without soy extract. Plasma concentrations of losartan and E-3174 were determined by liquid chromatography-tandem mass spectrometry for 12 and 24 hours, respectively. On day 8 through day 21 of the study, following a 7-day washout period, each subject consumed two 1000-mg Genistein Soy Complex tablets orally after meals, twice daily, for 14 days. On day 22, all volunteers received losartan 50 mg and blood samples were collected again. All subjects completed the study, without adverse drug effects. Over the 14-day pretreatment period, soy extract did not significantly influence the pharmacokinetics of losartan or E-3174. The ratio of the area under the curve of the drug and metabolite after losartan administration, with and without soy extract ingestion, was 0.21 +/- 0.05 and 0.23 +/- 0.05 (mean +/- SD), respectively. The difference was not statistically significant (p = 0.22). Our data indicate that a significant interaction between soy extract and losartan is unlikely to occur in females.