scholarly journals Investigation of a Potential Pharmacokinetic Interaction Between Nebivolol and Fluvoxamine in Healthy Volunteers

2017 ◽  
Vol 20 ◽  
pp. 68 ◽  
Author(s):  
Ana-Maria Gheldiu ◽  
Laurian Vlase ◽  
Adina Popa ◽  
Corina Briciu ◽  
Dana Muntean ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Heart Rate ◽  
Single Dose ◽  
Healthy Volunteers ◽  
Active Metabolite ◽  
Pharmacokinetic Interaction ◽  
Compartmental Analysis ◽  
Pharmacokinetic Parameters ◽  
Open Label ◽  
Hydroxylated Metabolite

Purpose: To investigate whether fluvoxamine coadministration can influence the pharmacokinetic properties of nebivolol and its active hydroxylated metabolite (4-OH-nebivolol) and to assess the consequences of this potential pharmacokinetic interaction upon nebivolol pharmacodynamics. Methods: This open-label, non-randomized, sequential clinical trial consisted of two periods: Period 1 (Reference), during which each volunteer received a single dose of 5 mg nebivolol and Period 2 (Test), when a combination of 5 mg nebivolol and 100 mg fluvoxamine was given to all subjects, after a 6-days pretreatment regimen with fluvoxamine (50-100 mg/day). Non-compartmental analysis was used to determine the pharmacokinetic parameters of nebivolol and its active metabolite. The pharmacodynamic parameters (blood pressure and heart rate) were assessed at rest after each nebivolol intake, during both study periods. Results: Fluvoxamine pretreatment increased Cmax and AUC0-∞  of nebivolol (Cmax: 1.67 ± 0.690  vs 2.20 ± 0.970  ng/mL; AUC0-∞: 12.1 ± 11.0  vs 19.3 ± 19.5  ng*h/mL ) and of its active metabolite (Cmax: 0.680  ± 0.220  vs 0.960 ± 0.290  ng/mL; AUC0-∞: 17.6 ±20.1  vs 25.5 ± 29.9  ng*h/mL). Apart from Cmax,AUC0-t and AUC0-∞, the other pharmacokinetic parameters (tmax, kel and t½) were not significantly different between study periods. As for the pharmacodynamic analysis, decreases in blood pressure and heart rate after nebivolol administration were similar with and without fluvoxamine concomitant intake. Conclusions: Due to enzymatic inhibition, fluvoxamine increases the exposure to nebivolol and its active hydroxylated metabolite in healthy volunteers. This did not influence the blood pressure and heart-rate lowering effects of the beta-blocker administered as single-dose. However, more detail studies involving actual patients are required to further investigate the clinical relevance of this drug interaction. This article is open to POST-PUBLICATION REVIEW. Registered readers (see “For Readers”) may comment by clicking on ABSTRACT on the issue’s contents page.

scholarly journals Phenotypic differences in nebivolol metabolism and bioavailability in healthy volunteers

2015 ◽  
Vol 88 (2) ◽  
pp. 208-213 ◽  
Author(s):  
Corina Briciu ◽  
Maria Neag ◽  
Dana Muntean ◽  
Corina Bocsan ◽  
Anca Buzoianu ◽  
...  
Keyword(s):  
Healthy Volunteers ◽  
Active Metabolite ◽  
Genetic Regulation ◽  
Standard Normal Distribution ◽  
Pharmacokinetic Analysis ◽  
Pharmacokinetic Parameters ◽  
Open Label ◽  
Phenotypic Differences ◽  
Standard Normal ◽  
Unique Distribution

Introduction: Nebivolol, a third-generation β-blocker, is subject to extensive first-pass metabolism and produces active β-blocking hydroxylated metabolites, like 4-OH-nebivolol. It is primarily a substrate of CYP2D6, a metabolic pathway that is under polymorphic genetic regulation. The objective of this study was to assess the metabolizer phenotype and to evaluate the interphenotype bioavailability and metabolism of nebivolol.Material and methods: Forty-three healthy volunteers were included in this open-label, non-randomized clinical trial and each volunteer received a single dose of 5 mg nebivolol. Non-compartmental pharmacokinetic analysis was performed to determine the pharmacokinetic parameters of nebivolol and its active metabolite. The phenotypic distribution was assessed based on the AUC (aria under the curve) metabolic ratio of nebivolol/4-OH-nebivolol and statistical analysis. An interphenotype comparison of nebivolol metabolism and bioavailability was performed based on the pharmacokinetic parameters of nebivolol and its active metabolite.Results: Nebivolol/4-OH-nebivolol AUC metabolic ratios were not characterized by a standard normal distribution. The unique distribution emphasized the existence of two groups and the 43 healthy volunteers were classified as follows: poor metabolizers (PMs)=3, extensive metabolizers (EMs)=40. The phenotype had a marked impact on nebivolol metabolism. The exposure to nebivolol was 15-fold greater for PMs in comparison to EMs.  Conclusion: 40 EMs and 3 PMs were differentiated by using the pharmacokinetic parameters of nebivolol and its active metabolite. The study highlighted the existence of interphenotype differences regarding nebivolol metabolism and bioavailability.

scholarly journals The Bioavailability and Pharmacokinetics of Silymarin SMEDDS Formulation Study in Healthy Thai Volunteers

2018 ◽  
Vol 2018 ◽  
pp. 1-7 ◽  
Author(s):  
Chuleegone Sornsuvit ◽  
Darunee Hongwiset ◽  
Songwut Yotsawimonwat ◽  
Manatchaya Toonkum ◽  
Satawat Thongsawat ◽  
...  
Keyword(s):  
Single Dose ◽  
Healthy Volunteers ◽  
Pharmacokinetic Study ◽  
Oral Bioavailability ◽  
Pharmacokinetic Parameters ◽  
Open Label ◽  
Blood Samples ◽  
Rapid Absorption ◽  
The Mean

The present study aimed to determine the pharmacokinetic parameters and bioavailability of silymarin 140 mg SMEDDS formulation. An open-label, single-dose pharmacokinetic study was conducted. Twelve healthy volunteers were included in the study. After the volunteers had fasted overnight for 10 h, a single-dose generic silymarin 140 mg SMEDDS soft capsule was administered. Then 10 ml blood samples were taken at 0.0, 0.25, 0.50, 0.75, 1.0, 1.33, 1.67, 2.0, 2.5, 3.0, 4.0, 6.0, 8.0, 10.0, and 12.0 h. The plasma silybin concentrations were analyzed using validated LC-MS/MS. The pharmacokinetic parameters were analyzed and calculated. The pharmacokinetic parameters were calculated after silymarin had been administered as a single capsule. The mean (range) Cmax was 812.43 (259.47–1505.47) ng/ml at 0.80 (0.25–1.67) h (tmax). The mean (range) AUC0-t and AUC0-inf were 658.80 (268.29–1045.01) ng.h/ml and 676.98 (274.10–1050.96) ng.h/ml, respectively. The mean ke and t1/2 were 0.5386 h-1 and 1.91 h, respectively. The silymarin SMEDDS formulation soft capsule showed rapid absorption and high oral bioavailability.

scholarly journals Bioequivalence study of different brands of vildagliptin in healthy human subjects

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Mahaveer Sharma ◽  
S. S. Agrawal
Keyword(s):  
Single Dose ◽  
Healthy Volunteers ◽  
Geometric Mean ◽  
Bioequivalence Study ◽  
Pharmacokinetic Parameters ◽  
Open Label ◽  
Healthy Human ◽  
Single Dose Study ◽  
Dipeptidyl Peptidase 4 ◽  
Significant Difference

Abstract Background Vildagliptin is a dipeptidyl peptidase-4 inhibitor used to treat diabetes mellitus. No bioequivalence study data have been published for the Indian population comparing bioequivalence of vildagliptin brands Galvus, Zomelis, and Jalra. This study aimed to evaluate the bioequivalence between three brands of vildagliptin 50 mg tablet (test 1, Zomelis; test 2, Jalra; and reference, Galvus) and to compare these test formulations with the reference formulation to meet the regulatory requirements of bioequivalence of CDSCO, India. The study was conducted in the clinical research center of the college after enrolling 12 healthy volunteers. This study was a single-dose, randomized, open-label, balanced, three treatment, three period, under fasting condition in 12 adult healthy volunteers. After overnight fasting, the subjects received a single dose of either of any three brands of the vildagliptin tablet (T1—test 1; T2—test 2; and R—reference). The washout period was 7 days. Randomization was in the way of T1T2R in the first period, T2T1R in the second period, and RT1T2 in the third period. Blood samples were collected, after that drug concentration in the plasma was measured with the help of HPLC. Outcome measures 90% confidence interval of the geometric mean ratios (test/reference) for the LnCmax, LnAUC0-t, and LnAUC0-∞ was calculated. Results The AUC0-t was 1390.03, 1401.50, and 1409.37 ng h/ml for the T1, T2, and R, respectively. Cmax was 287.89, 287.41, and 285.17 ng/ml for the T1, T2, and R, respectively. AUC0-∞ was 1452.03, 1467.59, and 1473.53 ng h/ml for the T1, T2, and R, respectively. No significant difference was observed in the pharmacokinetic parameters between the T1, T2, and R. The geometric mean ratios for T1/R for LnCmax, LnAUC0-t, and LnAUC0-∞ were 1.0014 (90% CI, 1.0002–1.0026), 0.9992 (90% CI, 0.9971–1.0013), and 0.9994 (90% CI, 0.9973–1.0016), respectively. For the T2/R, geometric mean ratios for LnCmax, LnAUC0-t, and LnAUC0-∞ were 1.0003 (90% CI, 0.9992–1.0013), 0.9988 (90% CI, 0.9969–1.0008), and 0.9985 (90% CI, 0.9961–1.0010), respectively. Conclusion In this single-dose study involving Indian healthy volunteers under fasting conditions, the three brands of vildagliptin (Zomelis, Jalra, and Galvus) were bioequivalent as per the bioequivalence criterion of CDSCO, India.

scholarly journals BIOEQUIVALENCE STUDY OF AZELNIDIPINE 16 MG TABLET TO EVALUATE PHARMACOKINETIC PROFILE OF SINGLE DOSE IN HEALTHY, ADULT, HUMAN VOLUNTEERS UNDER FASTING CONDITION

2021 ◽  
pp. 154-159
Author(s):  
DIBYA DAS ◽  
DHIMAN HALDER ◽  
ANIRBANDEEP BOSE ◽  
CHIRANJIT SAHA ◽  
HIMANGSHU SEKHAR MAJI ◽  
...  
Keyword(s):  
Single Dose ◽  
Healthy Volunteers ◽  
Plasma Sample ◽  
Reference Product ◽  
Bioequivalence Study ◽  
Pharmacokinetic Parameters ◽  
Open Label ◽  
Entire Study ◽  
Test Product ◽  
Fasting Condition

Objective: The present study's objective is to conduct a comparative bioavailability study with a special emphasis on the test product's bioequivalence using a standard reference product as a comparator. Methods: Before initiating the bioequivalent study, the plasma sample analysis method was developed and validated by using LC-MS/MS method. The entire study was conducted as a single-dose crossover randomized bioequivalence study with open-label, two treatment, two-period, and two sequences on 24 healthy volunteers under fasting condition. With proper informed consent process the oral dose of the Reference product (R) or Test product (T) was administered on healthy volunteers at 0 h during each period of the study. After the drug's oral administration, a certain quantity of blood sample was collected, and the plasma sample was separated using a cold centrifuge. The plasma samples were analysed by using the validated LC-MS/MS method. The pharmacokinetic parameters, statistical data and ANOVA of the test and reference product were evaluated. Results: The Cmax, Auc0-t, AUC0-∞ and tmax of the test product were found to be 6.29 ng/ml, 117.0 ng. h/ml, 161.67 ng. h/ml and 3.33 h. respectively. And the Cmax, Auc0-t, AUC0-∞ and tmax of reference product were found 6.59 ng/ml, 123.21 ng. h./ml, 172.20 ng. h/ml and 3.38 h respectively. Relative bioavailability was found 94.96%. The overall results show that the 90% confidence intervals (Log-Transformed and Untransformed) for Cmax, AUC0-t and AUC0-∞ for Azelnidipine were within the acceptable limit of 80%-125%. Conclusion: The entire study's conclusion can be drawn as the test product was bioequivalent with the reference product's comparator.

An Evaluation of the Potential for Pharmacokinetic Interaction between Tramadol and Cytochrome P450 2D6 Inhibitor Promethazine

2014 ◽  
Vol 989-994 ◽  
pp. 1041-1043
Author(s):  
Ping Liu ◽  
Liang Sun ◽  
Jian Zhang ◽  
Rui Chen Guo
Keyword(s):  
Single Dose ◽  
Plasma Concentration ◽  
Pharmacokinetic Interaction ◽  
Apparent Volume ◽  
Volume Of Distribution ◽  
Pharmacokinetic Parameters ◽  
Maximum Plasma ◽  
Open Label ◽  
Tramadol Hydrochloride ◽  
Time Curve

In this single-center, randomized, open-label, 3-way crossover study, subjects received each of the following: a single dose of Tramadol Hydrochloride Injection (THI) 35 mg, a single dose of Promethazine Hydrochloride Injection (PHI) 45 mg, and single dose of Compound Tramadol Hydrochloride Injection (CTHI) 80mg. Blood was collected and plasma was analyzed for the pharmacokinetic parameters (maximum plasma concentration [Cmax], time to Cmax [Tmax], area under the plasma concentration-time curve, plasma elimination half-life, clearance, and apparent volume of distribution) of Tramadol and Promethazine. In general, several pharmacokinetic interactions were observed between Tramadol and Promethazine in the present study.

Compression Stocking Length Effects on Arterial Blood Pressure and Heart Rate Following Head-Up Tilt in Healthy Volunteers

2014 ◽  
Vol 63 (6) ◽  
pp. 435-438 ◽  
Author(s):  
Kunihiko Tanaka ◽  
Shiori Tokumiya ◽  
Yumiko Ishihara ◽  
Yumiko Kohira ◽  
Tetsuro Katafuchi
Keyword(s):  
Blood Pressure ◽  
Heart Rate ◽  
Healthy Volunteers ◽  
Arterial Blood Pressure ◽  
Compression Stocking ◽  
Arterial Blood ◽  
Head Up Tilt ◽  
Length Effects

Effects of S-adenosyl-methionine on plasma norepinephrine, blood pressure, and heart rate in healthy volunteers

1986 ◽  
Vol 17 (2) ◽  
pp. 111-118 ◽  
Author(s):  
Michael A. Sherer ◽  
Giulio L. Cantoni ◽  
Robert N. Golden ◽  
Matthew V. Rudorfer ◽  
William Z. Potter
Keyword(s):  
Blood Pressure ◽  
Heart Rate ◽  
Healthy Volunteers ◽  
Plasma Norepinephrine ◽  
Adenosyl Methionine

Comparative study on effect of neutral spinal bath and neutral spinal spray on blood pressure, heart rate and heart rate variability in healthy volunteers

2018 ◽  
Vol 16 (2) ◽  
Author(s):  
Arundhati Goley ◽  
A. Mooventhan ◽  
NK. Manjunath
Keyword(s):  
Blood Pressure ◽  
Heart Rate ◽  
Heart Rate Variability ◽  
Healthy Volunteers ◽  
Group Analysis ◽  
Low Frequency ◽  
Single Session ◽  
Arterial Blood ◽  
Before And After ◽  
Instantaneous Heart Rate

Abstract Background Hydrotherapeutic applications to the head and spine have shown to improve cardiovascular and autonomic functions. There is lack of study reporting the effect of either neutral spinal bath (NSB) or neutral spinal spray (NSS). Hence, the present study was conducted to evaluate and compare the effects of both NSB and NSS in healthy volunteers. Methods Thirty healthy subjects were recruited and randomized into either neutral spinal bath group (NSBG) or neutral spinal spray group (NSSG). A single session of NSB, NSS was given for 15 min to the NSBG and NSSG, respectively. Assessments were taken before and after the interventions. Results Results of this study showed a significant reduction in low-frequency (LF) to high-frequency (HF) (LF/HF) ratio of heart rate variability (HRV) spectrum in NSBG compared with NSSG (p=0.026). Within-group analysis of both NSBG and NSSG showed a significant increase in the mean of the intervals between adjacent QRS complexes or the instantaneous heart rate (HR) (RRI) (p=0.002; p=0.009, respectively), along with a significant reduction in HR (p=0.002; p=0.004, respectively). But, a significant reduction in systolic blood pressure (SBP) (p=0.037) and pulse pressure (PP) (p=0.017) was observed in NSSG, while a significant reduction in diastolic blood pressure (DBP) (p=0.008), mean arterial blood pressure (MAP) (p=0.008) and LF/HF ratio (p=0.041) was observed in NSBG. Conclusion Results of the study suggest that 15 min of both NSB and NSS might be effective in reducing HR and improving HRV. However, NSS is particularly effective in reducing SBP and PP, while NSB is particularly effective in reducing DBP and MAP along with improving sympathovagal balance in healthy volunteers.

Pharmacokinetics and bioequivalence of generic etoricoxib in healthy volunteers

2021 ◽  
Vol 10 (3) ◽  
pp. 113-118
Author(s):  
Nishalini Harikrishnan ◽  
Ka-Liong Tan ◽  
Kar Ming Yee ◽  
Alia Shaari Ahmad Shukri ◽  
Nalla Ramana Reddy ◽  
...  
Keyword(s):  
Compartmental Analysis ◽  
Bioequivalence Study ◽  
Active Pharmaceutical Ingredient ◽  
Pharmacokinetic Profile ◽  
Time Profile ◽  
Pharmacokinetic Parameters ◽  
Open Label ◽  
Reference Drug ◽  
Test Formulation ◽  
R Ratio

Introduction/Study Objectives: A bioequivalence study was performed to compare the pharmacological profile of innovator etoricoxib (ETO) with a newly developed generic ETO, both in a 120 mg tablet formulation. A dissolution study was conducted to optimize the formulation process before evaluating physical changes in the active pharmaceutical ingredient and the formulated product. Methods: This was a randomized, open-label, balanced, two-treatment, two-period, two-sequence, single-dose, two-way crossover, truncated bioequivalence study involving a washout period of ten days. A total of 26 healthy male volunteers were recruited. The pharmacokinetic profile of the test formulation was compared with the reference formulation. Results/Discussion: The pharmacokinetic parameters of ETO were calculated based on the plasma drug concentration-time profile using non-compartmental analysis to determine its safety profile and tolerability. The Test/Reference (T/R) ratio of ETO was 104.36% (90% confidence interval (CI): 98.30%–110.80%) for area under curve (AUC)0-72 while the T/R ratio of maximum concentration (Cmax) was 101.39% (92.15%–111.56%). The 90% CI of the Cmax and AUC0-72 of ETO were within acceptable bioequivalence limits of 80%–125%. All values were within the predetermined limits of the Association of Southeast Asian Nation (ASEAN) bioequivalence guidelines. Conclusion: The test formulation was found to be bioequivalent with respect to the reference drug, according to ASEAN bioequivalence guidelines.

scholarly journals Similar Results in Children with Asthma for Steady State Pharmacokinetic Parameters of Ciclesonide Inhaled with or without Spacer

2010 ◽  
Vol 4 ◽  
pp. CMPed.S4311 ◽  
Author(s):  
H. Boss ◽  
P. Minic ◽  
R. Nave
Keyword(s):  
Active Metabolite ◽  
Day Treatment ◽  
Systemic Exposure ◽  
Dose Inhaler ◽  
Pharmacokinetic Parameters ◽  
Metered Dose Inhaler ◽  
Inhaled Corticosteroid ◽  
Open Label ◽  
Metered Dose ◽  
Children With Asthma

Background Ciclesonide is an inhaled corticosteroid administered by a metered dose inhaler (MDI) to treat bronchial asthma. After inhalation, the inactive ciclesonide is converted by esterases in the airways to active metabolite desisobutyryl-ciclesonide (des-CIC). Aim To compare the pharmacokinetic (PK) parameters of des-CIC in children after administration of therapeutic dose of ciclesonide with and without spacer (AeroChamber Plus™). Methods Open-label, 3 period, cross over, repeated dose, PK study in 37 children with mild to moderate stable asthma (age: 6–11 y; body weight: 20–53 kg). During each 7-day treatment period, ciclesonide was inhaled once in the morning: A) 160 μg MDI with spacer, B) 80 μg MDI with spacer, and C) 160 μg MDI without spacer. Serum PK parameters of ciclesonide and des-CIC were determined on Day 7 of each period. The primary PK parameters were the AUCτ and Cmax for des-CIC. Results Inhaling ciclesonide with spacer led to a dose proportional systemic exposure (AUCτ) of des-CIC (0.316 μg*h/L for 80 μg and 0.663 μg*h/L for 160 μg). The dose-normalized systemic exposure for des-CIC (based on AUCτ) was 27% higher after inhalation of ciclesonide 80 μg or 160 μg with spacer than without spacer; the corresponding Cmax values for des-CIC were, respectively, 63% and 55% higher with spacer. No clinically relevant abnormalities or adverse drug reactions were observed. Conclusions Inhalation of therapeutic ciclesonide dose with spacer led to a slight increase in the systemic exposure of des-CIC, which does not warrant dose adjustment.

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