Pharmacokinetic of Rhein in Healthy Male Volunteers Following Oral and Retention Enema Administration of Rhubarb Extract: A Single Dose Study

2005 ◽  
Vol 33 (06) ◽  
pp. 839-850 ◽  
Author(s):  
Wei Zhu ◽  
Xue-Mei Wang ◽  
Li Zhang ◽  
Xiao-Ye Li ◽  
Bao-Xiu Wang
Keyword(s):  
Single Dose ◽  
Oral Administration ◽  
Dosage Adjustment ◽  
Pharmacokinetic Parameters ◽  
Healthy Male ◽  
Single Dose Study ◽  
Retention Enema ◽  
Healthy Male Volunteers ◽  
Male Volunteers ◽  
Dose Study

Rhubarb is a common herb used in traditional Chinese medicine. However, few publications exist about its pharmacokinetic profiles in animals or healthy volunteers. Whether retention enema administration of rhubarb extract affects its pharmacokinetics as well as its tolerability is unknown. Therefore, we set out to compare the pharmacokinetic parameters of rhein administered by retention enemas with those of conventional oral dosing of rhubarb extract. Eight healthy male volunteers were enrolled in a prospective crossover study. All subjects received a single dose of rhubarb extract (50 mg·kg-1) on two separate occasions, once orally, once by a retention enema. Rhein plasma concentration was measured by HPLC. The C max , AUC 0-∞, AUMC were significantly higher in oral administration than those in retention enema administration ( p < 0.05), while V d of rhein after oral administration of rhubarb extract was significantly lower ( p < 0.05) than that after retention enema administration. However, no statistically significant differences between the two treatments were observed for any of the other pharmacokinetic parameters ( T max , t 1/2, MRT 0-∞, CL ). Dosage adjustment is advisable for retention enema administration of rhubarb extract in patients.

Liquid Chromatography-Tandem Mass Spectrometry Method for Ticagrelor and its Active Metabolite Determination in Human Plasma: Application to a Pharmacokinetic Study

2020 ◽  
Vol 16 (5) ◽  
pp. 602-608
Author(s):  
Niloufar Marsousi ◽  
Serge Rudaz ◽  
Jules A. Desmeules ◽  
Youssef Daali
Keyword(s):  
Clinical Trial ◽  
Formic Acid ◽  
Human Plasma ◽  
Active Metabolite ◽  
Pharmacokinetic Parameters ◽  
Pharmacokinetic Studies ◽  
Healthy Male ◽  
Coronary Syndrome ◽  
Healthy Male Volunteers ◽  
Male Volunteers

Background: Ticagrelor is a highly recommended new antiplatelet agent for the treatment of patients with acute coronary syndrome at moderate or high ischemic risk. There is a real need for rapid and accurate analytical methods for ticagrelor determination in biological fluids for pharmacokinetic studies. In this study, a sensitive and specific LC-MS method was developed and validated for quantification of ticagrelor and its Active Metabolite (AM) in human plasma over expected clinical concentrations. Methods: Samples were handled by Liquid-Liquid Extraction (LLE). A linear gradient was applied with a mobile phase composed of formic acid 0.1% and acetonitrile with 0.1% of formic acid using a C18 reversed-phase column. MS spectra were obtained by electrospray ionization in negative mode and optimized at 521.4→360.9 m/z, 477.2→361.2 m/z and 528.1→367.9 m/z transitions for ticagrelor, AM and ticagrelor-d7, respectively. Results: This method allowed rapid elution, in less than 4 minutes, and quantification of concentrations as low as 2 ng/mL for ticagrelor and 1 ng/mL for AM using only 100 μL of human plasma. LLE using hexane/ethyl acetate (50/50) was an optimal compromise in terms of extraction recovery and endogenous compounds interference. Trueness values of 87.8% and 89.5% and precisions of 84.1% and 93.8% were obtained for ticagrelor and AM, respectively. Finally, the usefulness of the method was assessed in a clinical trial where a single 180 mg ticagrelor was orally administered to healthy male volunteers. Pharmacokinetic parameters of ticagrelor and its active metabolite were successfully determined. Conclusion: A sensitive and specific quantification LC-MS-MS method was developed and validated for ticagrelor and its active metabolite determination in human plasma. The method was successfully applied to a clinical trial where a single ticagrelor 180 mg dose was orally administered to healthy male volunteers. The described method allows quantification of concentrations as low as 2 ng/mL of ticagrelor and 1 ng/mL of the metabolite using only 100 μL of plasma.

scholarly journals A first‐in‐human oral dose study of mesdopetam (IRL790) to assess its safety, tolerability, and pharmacokinetics in healthy male volunteers

2021 ◽  
Vol 9 (3) ◽  
Author(s):  
Folke Sjöberg ◽  
Susanna Waters ◽  
Boel Löfberg ◽  
Clas Sonesson ◽  
Nicholas Waters ◽  
...  
Keyword(s):  
Oral Dose ◽  
Healthy Male ◽  
Healthy Male Volunteers ◽  
Male Volunteers ◽  
Dose Study

Biological response genes after single dose administration of interferon β-1b to healthy male volunteers

2008 ◽  
Vol 199 (1-2) ◽  
pp. 115-125 ◽  
Author(s):  
Jan Hilpert ◽  
Johanna M. Beekman ◽  
Susanne Schwenke ◽  
Kristin Kowal ◽  
David Bauer ◽  
...  
Keyword(s):  
Single Dose ◽  
Biological Response ◽  
Healthy Male ◽  
Interferon Β ◽  
Dose Administration ◽  
Single Dose Administration ◽  
Healthy Male Volunteers ◽  
Male Volunteers

scholarly journals Safety, Tolerability, and Pharmacokinetics of PA-824 in Healthy Subjects

2009 ◽  
Vol 53 (9) ◽  
pp. 3720-3725 ◽  
Author(s):  
Ann M. Ginsberg ◽  
Martino W. Laurenzi ◽  
Doris J. Rouse ◽  
Karl D. Whitney ◽  
Melvin K. Spigelman
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Single Dose ◽  
Healthy Subjects ◽  
Multiple Dose ◽  
Pharmacokinetic Parameters ◽  
Blood Levels ◽  
Drug Resistant ◽  
Single Dose Study ◽  
Multiple Dose Study ◽  
Dose Study

ABSTRACT PA-824 is a novel antibacterial agent that has shown in vitro activity against both drug-sensitive and drug-resistant Mycobacterium tuberculosis. The compound's MIC is between 0.015 and 0.25 μg/ml for drug-sensitive strains and between 0.03 and 0.53 μg/ml for drug-resistant strains. In addition, it is active against nonreplicating anaerobic Mycobacterium tuberculosis. The safety, tolerability, and pharmacokinetics of PA-824 were evaluated in two escalating-dose clinical studies, one a single-dose study and the other a multiple-dose study (up to 7 days of daily dosing). In 58 healthy subjects dosed with PA-824 in these studies, the drug candidate was well tolerated, with no significant or serious adverse events. In both studies, following oral administration PA-824 reached maximal plasma levels in 4 to 5 h independently of the dose. Maximal blood levels averaged approximately 3 μg/ml (1,500-mg dose) in the single-dose study and 3.8 μg/ml (600-mg dose) in the multiple-dose study. Steady state was achieved after 5 to 6 days of daily dosing, with an accumulation ratio of approximately 2. The elimination half-life averaged 16 to 20 h. Overall, PA-824 was well tolerated following oral doses once daily for up to 7 days, and pharmacokinetic parameters were consistent with a once-a-day regimen. The results of these studies, combined with the demonstrated activity of PA-824 against drug-sensitive and multidrug-resistant Mycobacterium tuberculosis, support the investigation of this novel compound for the treatment of tuberculosis.

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