scholarly journals Urinary Elimination of Ecdysterone and Its Metabolites Following a Single-Dose Administration in Humans

Metabolites ◽  
2021 ◽  
Vol 11 (6) ◽  
pp. 366
Author(s):  
Gabriella Ambrosio ◽  
Tasha Yuliandra ◽  
Bernhard Wuest ◽  
Monica Mazzarino ◽  
Xavier de la Torre ◽  
...  
Keyword(s):  
Single Dose ◽  
Performance Enhancement ◽  
Estrogen Receptor Beta ◽  
Monitoring Program ◽  
Urine Samples ◽  
Dose Administration ◽  
Cumulative Urinary Excretion ◽  
First Order Kinetics ◽  
Mass Spectrometry Identification ◽  
Liquid Chromatography Tandem Mass

Ecdysterone is a phytosteroid widely discussed for its various pharmacological, growth-promoting, and anabolic effects, mediated by the activation of estrogen receptor beta (ERbeta). Performance-enhancement in sports was demonstrated recently, and ecdysterone was consequently included in the Monitoring Program, to detect potential patterns of misuse in sport. Only few studies on the pharmacokinetics of ecdysterone in humans have been reported so far. In this study, post-administration urine samples in twelve volunteers (single dose of 50 mg of ecdysterone) were analyzed using dilute-and-inject liquid-chromatography–tandem mass spectrometry. Identification and quantitation of ecdysterone and of two metabolites, 14-deoxy-ecdysterone and 14-deoxy-poststerone, was achieved. Ecdysterone was the most abundant analyte present in post-administration urine samples, detected for more than 2 days, with a maximum concentration (Cmax) in the 2.8–8.5 h urine (Cmax = 4.4–30.0 µg/mL). The metabolites 14-deoxy-ecdysterone and 14-deoxy-poststerone were detected later, reaching the maximum concentrations at 8.5–39.5 h (Cmax = 0.1–6.0 µg/mL) and 23.3–41.3 h (Cmax = 0.1–1.5 µg/mL), respectively. Sex-specific differences were not observed. Cumulative urinary excretion yielded average values of 18%, 2.3%, and 1.5% for ecdysterone, 14-deoxy-ecdysterone, and 14-deoxy-poststerone, respectively. Ecdysterone and 14-deoxy-ecdysterone were excreted following first-order kinetics with half-lives calculated with three hours, while pharmacokinetics of 14-deoxy-poststerone needs further evaluation.

scholarly journals Urinary Elimination of Ecdysterone and its Metabolites following a Single-Dose Administration in Humans

2021 ◽  
Author(s):  
Gabriella Ambrosio ◽  
Tasha Yuliandra ◽  
Bernhard Wuest ◽  
Monica Mazzarino ◽  
Xavier de la Torre ◽  
...  
Keyword(s):  
Single Dose ◽  
Performance Enhancement ◽  
Estrogen Receptor Beta ◽  
Monitoring Program ◽  
Dose Administration ◽  
Cumulative Urinary Excretion ◽  
First Order Kinetics ◽  
Mass Spectrometry Identification ◽  
Liquid Chromatography Tandem Mass ◽  
Receptor Beta

Ecdysterone is a phytosteroid widely discussed for its various pharmacological, growth-promoting and anabolic effects mediated by activation of estrogen receptor beta (ERbeta). Performance-enhancement in sports was demonstrated recently, and ecdysterone was consequently included in the Monitoring Program to detect potential patterns of misuse in sport. Only few studies on the pharmacokinetics of ecdysterone in humans have been reported so far. In this study, post-administration urines in twelve volunteers (single dose of 50 mg of ecdysterone) were analyzed using dilute-and-inject liquid chromatography-tandem mass spectrometry. Identification and quantitation of ecdysterone and of two metabolites, 14-deoxy ecdysterone and 14-deoxy poststerone was achieved. Ecdysterone was the most abundant analyte present in post-administration urines, detected for more than 2 days with a maximum concentration (Cmax) in the 2.8-8.5 h urines (Cmax = 4.4-30.0 µg/mL). The metabolites 14-deoxy ecdysterone and 14-deoxy poststerone were detected later reaching the maximum concentrations at 8.5-39.5 h (Cmax = 0.1-6.0 µg/mL) and 23.3-41.3 h (Cmax = 0.1-1.5 µg/mL), respectively. Cumulative urinary excretion yielded average values of 18%, 2.3% and 1.5% for ecdysterone, 14-deoxy ecdysterone and 14-deoxy poststerone, respectively. Ecdysterone and 14-deoxy ecdysterone were excreted following first order kinetics with half-lives calculated with three hours, while pharmacokinetics of 14-deoxy poststerone needs further evaluation.

scholarly journals Bio-Distribution and Pharmacokinetics of Topically Administered γ-Cyclodextrin Based Eye Drops in Rabbits

2021 ◽  
Vol 14 (5) ◽  
pp. 480
Author(s):  
Martin Kallab ◽  
Kornelia Schuetzenberger ◽  
Nikolaus Hommer ◽  
Bhavapriya Jasmin Schäfer ◽  
Doreen Schmidl ◽  
...  
Keyword(s):  
Single Dose ◽  
Drug Concentration ◽  
Vitreous Humor ◽  
Controlled Study ◽  
Eye Drops ◽  
Corneal Tissue ◽  
Single Administration ◽  
Local Tolerability ◽  
Dose Administration ◽  
Retinal Tissue

The purpose of this study was to evaluate the ocular pharmacokinetics, bio-distribution and local tolerability of γ-cyclodextrin (γCD) based irbesartan 1.5% eye drops and candesartan 0.15% eye drops after single and multiple topical administration in rabbit eyes. In this randomized, controlled study, a total number of 59 New Zealand White albino rabbits were consecutively assigned to two study groups. Group 1 (n = 31) received irbesartan 1.5% and group 2 (n = 28) candesartan 0.15% eye drops. In both groups, single dose and multiple administration pharmacokinetic studies were performed. Rabbits were euthanized at five predefined time points after single-dose administration, whereas multiple-dose animals were dosed for 5 days twice-daily and then euthanized 1 h after the last dose administration. Drug concentration was measured by using liquid chromatography-tandem mass spectrometry (LC-MS/MS) in the retinal tissue, vitreous humor, aqueous humor, corneal tissue and in venous blood samples. Pharmacokinetic parameters including maximal drug concentration (Cmax), time of maximal drug concentration (Tmax), half-life and AUC were calculated. To assess local tolerability, six additional rabbits received 1.5% irbesartan eye drops twice daily in one eye for 28 days. Tolerability was assessed using a modified Draize test and corneal sensibility by Cochet Bonnet esthesiometry. Both γCD based eye drops were rapidly absorbed and distributed in the anterior and posterior ocular tissues. Within 0.5 h after single administration, the Cmax of irbesartan and candesartan in retinal tissue was 251 ± 142 ng/g and 63 ± 39 ng/g, respectively. In the vitreous humor, a Cmax of 14 ± 16 ng/g for irbesartan was reached 0.5 h after instillation while Cmax was below 2 ng/g for candesartan. For multiple dosing, the observed Cmean in retinal tissue was 338 ± 124 ng/g for irbesartan and 36 ± 10 ng/g for candesartan, whereas mean vitreous humor concentrations were 13 ± 5 ng/g and <2 ng/g, respectively. The highest plasma concentrations of both irbesartan (Cmax 5.64 ± 4.08 ng/mL) and candesartan (Cmax 4.32 ± 1.04 ng/mL) were reached 0.5 h (Tmax) after single administration. Local tolerability was favorable with no remarkable differences between the treated and the control eyes. These results indicate that irbesartan and candesartan in γCD based nanoparticle eye drops can be delivered to the retinal tissue of the rabbit’s eye in pharmacologically relevant concentrations. Moreover, safety and tolerability profiles appear to be favorable in the rabbit animal model.

scholarly journals Efficacy and Safety of Mizoribine by One Single Dose Administration for Patients with Rheumatoid Arthritis

2010 ◽  
Vol 49 (20) ◽  
pp. 2211-2218 ◽  
Author(s):  
Kunihiro Ichinose ◽  
Tomoki Origuchi ◽  
Shin-ya Kawashiri ◽  
Naoki Iwamoto ◽  
Keita Fujikawa ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Single Dose ◽  
Efficacy And Safety ◽  
Dose Administration ◽  
Single Dose Administration

Bioavailability of Digoxin and Beta-Methyl-Digoxin

1976 ◽  
Vol 4 (5) ◽  
pp. 352-354
Author(s):  
L Padeletti ◽  
F Fantini ◽  
P Cinelli ◽  
C Gremigni
Keyword(s):  
Single Dose ◽  
Serum Concentration ◽  
Urinary Excretion ◽  
Crossover Study ◽  
Drug Absorption ◽  
Normal Volunteers ◽  
Cumulative Urinary Excretion ◽  
Serial Serum ◽  
Concentration Measurements ◽  
Randomized Crossover Study

In a randomized crossover study the bioavailability of a single dose of digoxin and of beta-methyl-digoxin tablets was tested in four normal volunteers. No difference was found between the two products in the rate and extent of drug absorption using 6 day cumulative urinary excretion and serial serum concentration measurements.

scholarly journals Quantitation of Benzodiazepines and Metabolites in Urine by Liquid Chromatography–Tandem Mass Spectrometry

2018 ◽  
Vol 3 (3) ◽  
pp. 397-407
Author(s):  
Yu Zi Zheng ◽  
Dustin R Bunch ◽  
Katherine Lembright ◽  
Sihe Wang
Keyword(s):  
Precise Measurement ◽  
High Sensitivity ◽  
Urine Samples ◽  
Limit Of Quantification ◽  
Internal Standards ◽  
Independent Laboratory ◽  
Chromatography Tandem Mass Spectrometry ◽  
Analytical Recovery ◽  
Liquid Chromatography Tandem Mass ◽  
Analytical Time

Abstract Background Benzodiazepines (BZDs) are central nervous system depressants that are prescribed to prevent seizures, manage anxiety, or help sleep. When misused, BZDs can lead to addiction and sometimes cause death. Measurement of BZDs in urine is used to identify their use, especially in pain management settings. LC-MS/MS is preferred for these measurements because of its high sensitivity and specificity. Here, we report an LC-MS/MS assay for measuring 7 BZDs and metabolites in urine. Methods Urine sample was incubated at 60 °C for 30 min after addition of internal standards and a β-glucuronidase solution. After centrifugation, the supernatant was diluted with methanol and water before being injected onto a C18 analytical column in an LC-MS/MS system for quantification. The analytical time between injections was 4.35 min. The analytes included 7-aminoclonazepam, α-hydroxyalprazolam, α-hydroxytriazolam, oxazepam, lorazepam, nordiazepam, and temazepam. Results The lower limit of quantification ranged from 30 ng/mL to 50 ng/mL with an analytical recovery &gt;80% for all 7 analytes. Total CV was &lt;10% for all analytes (3 concentration levels of 100, 2500, and 5000 ng/mL; n = 30 each). This method had 100% agreement with a GC-MS method offered by an independent laboratory for negative urine samples. For the positive urine samples, this method showed a strong correlation (R &gt; 0.96) with the GC-MS method. Conclusions The LC-MS/MS assay allows accurate and precise measurement of 7 BZDs and metabolites in a single analytical run with a short analytical run time and broad measuring ranges.

scholarly journals Pharmacokinetics and Safety of Intravenous Ceftolozane-Tazobactam in Healthy Adult Subjects following Single and Multiple Ascending Doses

2012 ◽  
Vol 56 (6) ◽  
pp. 3086-3091 ◽  
Author(s):  
Benjamin Miller ◽  
Ellie Hershberger ◽  
David Benziger ◽  
MyMy Trinh ◽  
Ian Friedland
Keyword(s):  
Single Dose ◽  
Adverse Events ◽  
Healthy Adult ◽  
Volume Of Distribution ◽  
Dose Administration ◽  
Mean Values ◽  
Multiple Doses ◽  
Dosing Regimens ◽  
Dose Levels ◽  
Dose Limiting Toxicity

ABSTRACTThe pharmacokinetics and safety of ceftolozane, a novel cephalosporin, and tazobactam, a β-lactamase inhibitor, alone and in combination as a 2:1 ratio in single doses of up to 2,000 and 1,000 mg of ceftolozane and tazobactam, respectively, and multiple doses of up to 3,000 and 1,500 mg of ceftolozane and tazobactam, respectively, per day were evaluated in healthy adult subjects. In part 1, groups of six subjects each received single ascending doses of ceftolozane, tazobactam, and ceftolozane-tazobactam in a within-cohort crossover design. In part 2, groups of 5 or 10 subjects each received multiple doses of ceftolozane, tazobactam, or ceftolozane-tazobactam for 10 days. After a single dose of ceftolozane alone, the ranges of mean values for half-life (2.48 to 2.64 h), the total clearance (4.35 to 6.01 liters/h), and the volume of distribution at steady state (11.0 to 14.1 liters) were consistent across dose levels and similar to those observed when ceftolozane was coadministered with tazobactam. Mean values after multiple doses for ceftolozane alone and ceftolozane-tazobactam were similar to those seen following a single dose. The pharmacokinetics of the dosing regimens evaluated were dose proportional and linear. Ceftolozane-tazobactam was well tolerated and systemic adverse events were uncommon. Mild infusion-related adverse events were the most commonly observed following multiple-dose administration. Adverse events were not dose related, and no dose-limiting toxicity was identified.

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