scholarly journals Effects of FMO3 Polymorphisms on Pharmacokinetics of Sulindac in Chinese Healthy Male Volunteers

2017 ◽  
Vol 2017 ◽  
pp. 1-7 ◽  
Author(s):  
Yong-Jun Tang ◽  
Kai Hu ◽  
Wei-Hua Huang ◽  
Chong-Zhi Wang ◽  
Zhi Liu ◽  
...  
Keyword(s):  
Plasma Concentrations ◽  
Pharmacokinetic Parameters ◽  
Healthy Male ◽  
Mean Values ◽  
Healthy Male Volunteers ◽  
Male Volunteers ◽  
Pcr Rflp ◽  
Hardy Weinberg Equilibrium ◽  
Sulindac Sulfide ◽  
The Mean

Sulindac is a nonsteroidal anti-inflammatory drug, which is clinically used for the ailments of various inflammations. This study investigated the allele frequencies of FMO3 E158K and E308G and evaluated the influences of these two genetic polymorphisms on the pharmacokinetics of sulindac and its metabolites in Chinese healthy male volunteers. Eight FMO3 wild-type (FMO3 HHDD) subjects and seven FMO3 homozygotes E158K and E308G mutant (FMO3 hhdd) subjects were recruited from 247 healthy male volunteers genotyped by PCR-RFLP method. The plasma concentrations of sulindac, sulindac sulfide, and sulindac sulfone were determined by UPLC, while the pharmacokinetic parameters of the two different FMO3 genotypes were compared with each other. The frequencies of FMO3 E158K and E308G were 20.3% and 20.1%, respectively, which were in line with Hardy-Weinberg equilibrium (D′ = 0.977, r2 = 0.944). The mean values of Cmax, AUC0–24, and AUC0–∞ of sulindac were significantly higher in FMO3 hhdd group than those of FMO3 HHDD group (P<0.05), while the pharmacokinetic parameters except Tmax of sulindac sulfide and sulindac sulfone showed no statistical difference between the two groups. The two FMO3 mutants were in close linkage disequilibrium and might play an important role in the pharmacokinetics of sulindac in Chinese healthy male volunteers.

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 Induction of theophylline clearance by rifampin and rifabutin in healthy male volunteers.

1996 ◽  
Vol 40 (8) ◽  
pp. 1866-1869 ◽  
Author(s):  
J G Gillum ◽  
J M Sesler ◽  
V L Bruzzese ◽  
D S Israel ◽  
R E Polk
Keyword(s):  
Treatment Phase ◽  
Pharmacokinetic Parameters ◽  
Theophylline Clearance ◽  
Healthy Male ◽  
Time Curve ◽  
Concentration Time ◽  
Male Volunteers ◽  
Hepatic Microsomal Enzyme ◽  
The Mean ◽  
To Receive

Rifampin and rifabutin induce the metabolism of many drugs, which may result in subtherapeutic concentrations and failure of therapy. However, differences between rifabutin and rifampin in potency of induction, and the specific enzymes which are altered, are not clear. This study, involving 12 adult male volunteers, compared the effects of 14-day courses of rifampin and rifabutin on clearance of theophylline, a substrate for the hepatic microsomal enzyme CYP1A2. Subjects were given oral theophylline solution (5 mg/kg of body weight) on day 1 and then randomized to receive daily rifampin (300 mg) or rifabutin (300 mg) on days 3 to 16. Theophylline was readministered as described above on day 15. The first treatment sequence was followed by a 2-week washout period; subjects then received the alternative treatment. Theophylline concentrations were determined for 46 h after each dose, and pharmacokinetic parameters were determined. One subject developed flu-like symptoms while taking rifabutin and withdrew voluntarily. Results from the remaining 11 subjects are reported. Compared with the baseline, the mean area under the concentration-time curve (AUC) (+/- standard deviation) for theophylline declined significantly following rifampin treatment (from 140 +/- 37 to 100 +/- 24 micrograms . h/ml, P <0.001); there was no significant change following rifabutin treatment (136 +/- 48 to 128 +/- 45 micrograms.h/ml). Baseline theophylline AUCs before each treatment phase were not different. A comparison of equal doses of rifampin and rifabutin administered to healthy volunteers for 2 weeks indicates that induction of CYP1A2, as measured by theophylline clearance, is significantly less following rifabutin treatment than it is following rifampin treatment. However, the relative induction potency for other metabolic enzymes remains to be investigated.

scholarly journals Pharmacokinetic Parameters of Ciprofloxacin in Bangladeshi Volunteers: A Preliminary Evaluation

2014 ◽  
Vol 27 (1-2) ◽  
pp. 1-8
Author(s):  
Reefat Zaman Chowdhury ◽  
Md Saiful Islam ◽  
Md Sayedur Rahman
Keyword(s):  
Healthy Volunteers ◽  
Oral Route ◽  
Absolute Bioavailability ◽  
Pharmacokinetic Parameters ◽  
Intravenous Route ◽  
Population Pharmacokinetic ◽  
Healthy Male ◽  
Healthy Male Volunteers ◽  
Male Volunteers ◽  
The Difference

The present study has attempted to establish a High-performance liquid chromatography (HPLC) method to determine ciprofloxacin in plasma, in order to evaluate the bioavailability of ciprofloxacin. In this study, initially 8 (eight) Bangladeshi Bangalee healthy male volunteers and 7 (seven) Bangladeshi Tribal healthy male volunteers received 500 mg tablet of pioneer brand of ciprofloxacin in oral route. Blood samples were collected at 0, 30, 60, 120, 180, 360, 540 and 720 minutes after drug administration. After 1 week of washout period, same volunteers of two groups received 200 mg injection of pioneer brand of ciprofloxacin in intravenous route. HPLC with ultraviolet detection was used to quantify plasma ciprofloxacin concentrations. In case of oral route, AUC0–12h, Cmax, Tmax and T1/2 values for Bangladeshi Bangalee and Tribal healthy volunteers were 545.53 ± 32.35 & 655.74 ± 16.57 ?g min/mL, 2.19 ± 0.16 & 2.49 ± 0.20 ?g/mL, 75.00 ± 27.77 & 94.29 ± 32.07 min and 241.96 ± 13.53 & 242.02 ± 19.88 min respectively. In case of intravenous route, the AUC0–12h, Cmax, Tmax and T1/2 values for Bangladeshi Bangalee and Tribal healthy volunteers were 344.07 ± 29.31 & 343.31 ± 25.34 ?g min/mL, 2.47 ± 0.17 & 2.46 ± 0.18 ?g/mL, 30.00 ± 0.00 & 30.0 ± 0.0 min and 278.16 ± 1.74 & 272.74 ± 4.42 min respectively and the difference between these two groups of volunteers was not significant. The difference in AUC0–12h, Cmax, Tmax and T1/2 values between these two groups of volunteers was significant. The mean percent absolute bioavailability in Bangladeshi Bangalee and Tribal healthy volunteers was 64.04 ± 3.21 and 76.81 ± 6.71 respectively. In conclusion, pharmacokinetic parameters of ciprofloxacin significantly varied among Bangladeshi Bangalee and Bangladeshi Tribal healthy volunteers indicating necessity of further study on population pharmacokinetic in these groups of people. DOI: http://dx.doi.org/10.3329/bjpp.v27i1-2.20066 Bangladesh J Physiol Pharmacol 2011;27(1&2):1-8.

scholarly journals A pharmacokinetics study of proposed bevacizumab biosimilar MYL-1402O vs EU-bevacizumab and US-bevacizumab

2021 ◽  
Author(s):  
Matthew Hummel ◽  
Tjerk Bosje ◽  
Andrew Shaw ◽  
Mark Shiyao Liu ◽  
Abhijit Barve ◽  
...  
Keyword(s):  
Serum Concentration ◽  
Phase 1 ◽  
Elimination Rate ◽  
Pharmacokinetic Analysis ◽  
Pharmacokinetic Parameters ◽  
Healthy Male ◽  
Double Blind ◽  
Healthy Male Volunteers ◽  
Male Volunteers ◽  
Eu And Us

Abstract Purpose Bevacizumab is a recombinant humanized monoclonal antibody that inhibits vascular endothelial growth factor-specific angiogenesis in some cancers. MYL-1402O is a proposed bevacizumab biosimilar. Methods The primary objective of this single-center, randomized, double-blind, three-arm, parallel-group, phase 1 study in healthy male volunteers was to evaluate bioequivalence of MYL-1402O to EU and US-reference bevacizumab, and EU-reference bevacizumab to US-reference bevacizumab. The primary pharmacokinetic parameter was area under the serum concentration–time curve from 0 extrapolated to infinity (AUC0–∞). Pharmacokinetic parameters were analyzed using general linear models of analysis of variance. Secondary endpoints included safety and tolerability. Results Of 111 enrolled subjects, 110 were included in the pharmacokinetic analysis (MYL-1402O, n = 37; EU-reference bevacizumab, n = 36; US-reference bevacizumab, n = 37). Bioequivalence was demonstrated between MYL-1402O and EU-reference bevacizumab, MYL-1402O and US-reference bevacizumab, and between EU- and US-reference bevacizumab where least squares mean ratios of AUC0–∞ were close to 1, and 90% CIs were within the equivalence range (0.80–1.25). Secondary pharmacokinetic parameters (AUC from 0 to time of last quantifiable concentration [AUC0–t], peak serum concentration [Cmax], time to Cmax, elimination rate constant, and elimination half-life) were also comparable, with 90% CIs for ratios of AUC0–t and Cmax within 80–125%. Treatment-emergent adverse events were similar across all three treatment groups and were consistent with clinical data for bevacizumab. Conclusion MYL-1402O was well tolerated and demonstrated pharmacokinetic and safety profiles similar to EU-reference bevacizumab and US-reference bevacizumab in healthy male volunteers. No new significant safety issues emerged (ClinicalTrials.gov, NCT02469987; ClinicalTrialsRegister.eu EudraCT, 2014-005621-12; June 12, 2015).

scholarly journals BIOEQUIVALENCE EVALUATION OF ORALLY DISINTEGRATING STRIPS OF RIZATRIPTAN IN MALE VOLUNTEERS UNDER FASTING CONDITIONS

2021 ◽  
pp. 230-235
Author(s):  
NIDHI SAPKAL ◽  
ANWAR DAUD ◽  
MINAL BONDE ◽  
MANGESH GAWANDE ◽  
NILAMBARI GURAV
Keyword(s):  
Statistical Analysis ◽  
Plasma Concentrations ◽  
Bioequivalence Study ◽  
Pharmacokinetic Analysis ◽  
Pharmacokinetic Parameters ◽  
Healthy Male ◽  
Treatment Results ◽  
Open Label ◽  
Male Volunteers ◽  
Extent Of Absorption

Objective: A randomized, open-label, balanced, two-treatment, two-period, two-sequence, single-dose, crossover bioequivalence study comparing Rizatriptan 10 mg Orally Disintegrating Strips (ODS, test) with that of established Oral Lyophilisate Rizatriptan 10 mg, Maxalt-MLT® (reference) was conducted in 24 healthy male volunteers under fasting conditions. A single oral dose of 10 mg Rizatriptan was administrated to each volunteer. Methods: Plasma concentrations of Rizatriptan were determined by a validated LC-MS/MS bioanalytical method. The plasma concentrations of Rizatriptan were considered for statistical analysis and for establishing bioequivalence. Pharmacokinetic analysis was done by using the non-compartmental method. Pharmacokinetic parameters Cmax, AUC0→t, AUC 0→∞, t1/2, Tmax, and Ke1 were estimated for each subject and each treatment. Results: Ninety percent confidence intervals (90% CI) calculated for the ratio of AUC0→t, AUC0→∞, and Cmax values for the test and reference formulations were 96.91-110.30%, 96.24-109.07%, and 90.37-113.56%, respectively for Rizatriptan. The 90% CIs of AUC0→t, AUC0→∞, and Cmax values were totally within 80-125%. Conclusion: Based on a statistical analysis of the results, both formulations of Rizatriptan 10 mg, were found to be bioequivalent in terms of rate and extent of absorption under fasting conditions.

Pharmacokinetics and metabolism of genaconazole, a potent antifungal drug, in men.

1996 ◽  
Vol 40 (1) ◽  
pp. 92-96 ◽  
Author(s):  
C Lin ◽  
H Kim ◽  
E Radwanski ◽  
M Affrime ◽  
M Brannan ◽  
...  
Keyword(s):  
Oral Dose ◽  
Single Oral Dose ◽  
Total Radioactivity ◽  
Healthy Male ◽  
Serum Samples ◽  
Time Curve ◽  
Concentration Time ◽  
Healthy Male Volunteers ◽  
Male Volunteers ◽  
The Mean

The pharmacokinetics of genaconazole, a racemic triazole antifungal agent comprising 50% RR and 50% SS enantiomers, were studied in 12 healthy male volunteers after a single oral dose of 200 mg. The serum samples were analyzed for the two enantiomers by using a chiral high-pressure liquid chromatography assay. The concentrations of the RR and SS enantiomers in serum were virtually identical. The mean values for the maximum concentrations in serum (Cmax) (1.7 micrograms/ml), times to Cmax (4.0 to 4.2 h), half-lives (83 h), and areas under the concentration-time curve from 0 h to infinity (195 to 199 micrograms.h/ml) were similar for the two enantiomers. The results showed that the pharmacokinetic profiles of the two enantiomers were similar after a single oral dosing of the racemate. The pharmacokinetics of the RR enantiomer were also evaluated in 12 healthy male volunteers after a single oral dose of 100 or 200 mg. The ratios of the Cmaxs and of the areas under the concentration-time curves from 0 h to infinity for the two doses were about 2, indicating a dose proportionality. In a separate study, six healthy male volunteers received a single oral dose of 50 mg of 14C-labeled genaconazole. The Cmax values for total radioactivity (14C) and intact genaconazole were virtually identical (0.6 micrograms/ml). The mean half-lives in serum were about 73 h for both total radioactivity and genaconazole. The amounts of total radioactivity excreted in the 0 to 240-h interval (representing approximately three half-lives) in urine and feces were 66.6 and 9.3% of the dose, respectively; 64.4% of the dose was excreted in urine as parent drug. There were no detectable metabolites in either serum or urine. The data demonstrate that genaconazole (racemate) is well absorbed, undergoes negligible biotransformation, and is slowly excreted, primarily in the urine.

scholarly journals Pharmacokinetics and Inflammatory-Fluid Penetration of Moxifloxacin following Oral or Intravenous Administration

1999 ◽  
Vol 43 (6) ◽  
pp. 1508-1510 ◽  
Author(s):  
Richard Wise ◽  
Jennifer M. Andrews ◽  
Gill Marshall ◽  
Giles Hartman
Keyword(s):  
Intravenous Administration ◽  
The Other ◽  
Healthy Male ◽  
Oral Dosing ◽  
Healthy Male Volunteers ◽  
Male Volunteers ◽  
Elimination Half ◽  
The Mean ◽  
Fluid Penetration

ABSTRACT A single 400-mg oral or intravenous (i.v.) dose of moxifloxacin was given to each of eight healthy male volunteers, and 6 weeks later the dose was administered by the other route. The concentrations of the drug in plasma, cantharidin-induced inflammatory fluid, and urine were measured over the subsequent 24 h. The mean maximum concentrations observed in plasma were 4.98 μg/ml after oral dosing and 5.09 μg/ml after i.v. dosing. The mean maximum concentrations attained in the inflammatory fluid were 2.62 and 3.23 μg/ml, respectively. The mean elimination half-lives from plasma were 8.32 and 8.17 h, respectively. The overall penetration into the inflammatory fluid was 103.4 and 104.2%. Over 24 h 15% of the drug was recovered in the urine when administered by either route.

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.

Glucocorticoid treatment is associated with dose-dependent insulin resistance in healthy male volunteers

2019 ◽  
Author(s):  
Riccardo Pofi ◽  
Ilaria Bonaventura ◽  
Nanthia Othonos ◽  
Thomas Marjot ◽  
Ahmed Moolla ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Healthy Male ◽  
Glucocorticoid Treatment ◽  
Healthy Male Volunteers ◽  
Male Volunteers ◽  
Dose Dependent
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