scholarly journals Pharmacokinetics, Safety, and Tolerability of Single-Dose Intravenous (ZTI-01) and Oral Fosfomycin in Healthy Volunteers

2017 ◽  
Vol 61 (9) ◽  
Author(s):  
E. Wenzler ◽  
E. J. Ellis-Grosse ◽  
K. A. Rodvold
Keyword(s):  
Single Dose ◽  
Oral Administration ◽  
Relative Bioavailability ◽  
Volume Of Distribution ◽  
Pharmacokinetic Parameters ◽  
Open Label ◽  
Time Curve ◽  
Blood And Urine Samples ◽  
Study Support ◽  
Tract Infections

ABSTRACT The pharmacokinetics, safety, and tolerability of intravenous (i.v.) fosfomycin disodium (ZTI-01) and oral fosfomycin tromethamine were evaluated after a single dose in 28 healthy adult subjects. Subjects received a single 1-h i.v. infusion of 1 g and 8 g fosfomycin disodium and a single dose of 3 g oral fosfomycin tromethamine in a phase I, randomized, open-label, three-period crossover study. Serial blood and urine samples were collected before and up to 48 h after dosing. The mean pharmacokinetic parameters ± standard deviations of fosfomycin in plasma after 1 g and 8 g i.v., respectively, were the following: maximum clearance of drug in serum (C max), 44.3 ± 7.6 and 370 ± 61.9 μg/ml; time to maximum concentration of drug in serum (T max), 1.1 ± 0.05 and 1.08 ± 0.01 h; volume of distribution (V), 29.7 ± 5.7 and 31.5 ± 10.4 liters; clearance (CL), 8.7 ± 1.7 and 7.8 ± 1.4 liters/h; renal clearance (CLR), 6.6 ± 1.9 and 6.3 ± 1.6 liters/h; area under the concentration-time curve from 0 to infinity (AUC0–∞), 120 ± 28.5 and 1,060 ± 192 μg·h/ml; and half-life (t 1/2), 2.4 ± 0.4 and 2.8 ± 0.6 h. After oral administration, the parameters were the following: C max, 26.8 ± 6.4 μg/ml; T max, 2.25 ± 0.4 h; V/F, 204 ± 70.7 liters; CL/F, 17 ± 4.7 liters/h; CLR, 6.5 ± 1.8 liters/h; AUC0–∞, 191 ± 57.6 μg · h/ml; and t 1/2, 9.04 ± 4.5 h. The percent relative bioavailability of orally administered fosfomycin was 52.8% in relation to the 1-g i.v. dose. Approximately 74% and 80% of the 1-g and 8-g i.v. doses were excreted unchanged in the urine by 48 h compared to 37% after oral administration, with the majority of this excretion occurring by 12 h regardless of dosage form. No new safety concerns were identified during this study. The results of this study support further investigation of i.v. fosfomycin in the target patient population, including patients with complicated urinary tract infections and pyelonephritis.

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.

scholarly journals Tigecycline Does Not Prolong Corrected QT Intervals in Healthy Subjects

2013 ◽  
Vol 57 (4) ◽  
pp. 1895-1901 ◽  
Author(s):  
Joan M. Korth-Bradley ◽  
Paul C. McGovern ◽  
Joanne Salageanu ◽  
Kyle Matschke ◽  
Anna Plotka ◽  
...  
Keyword(s):  
Healthy Subjects ◽  
Volume Of Distribution ◽  
Mixed Effects ◽  
Pharmacokinetic Parameters ◽  
Qtc Interval ◽  
Open Label ◽  
Time Curve ◽  
Linear Mixed Effects ◽  
Mixed Effects Modeling ◽  
Qt Intervals

ABSTRACTWe evaluated the effect of tigecycline (50-mg and 200-mg doses) on corrected QT (QTc) intervals and assessed safety and tolerability in a randomized, placebo-controlled, four-period crossover study of 48 (44 male) healthy volunteers aged 22 to 53 years. Fed subjects received tigecycline (50 mg or 200 mg) or placebo in a blinded fashion or an open-label oral dose of moxifloxacin (400 mg) after 1 liter of intravenous fluid. Serial electrocardiograms were recorded before, and for 96 h after, dosing. Blood samples for tigecycline pharmacokinetics were collected after each recording. QTc intervals were corrected using Fridericia's correction (QTcF). Pharmacokinetic parameters were calculated using noncompartmental methods with potential relationships examined using linear mixed-effects modeling. Adverse events were recorded. The upper limits of the 90% confidence interval for the mean difference between both tigecycline doses and placebo for all time-matched QTcF interval changes from baseline were <5 ms. The tigecycline concentrations initially declined rapidly and then more slowly. In the group given 50 mg of tigecycline, the pharmacokinetic parameters and means were as follows: maximum concentration of drug in serum (Cmax), 432 ng/ml; area under the concentration-time curve from time zero extrapolated to infinity (AUC0–∞), 2,366 ng · h/ml; clearance (CL), 21.1 liters/h; volume of distribution at steady state (Vss), 610 liters; and terminal half-life (t1/2), 22.1 h. Proportional or similar values were found for the group given 200 mg of tigecycline. Linear mixed-effects modeling failed to show an effect on QTcF values by tigecycline concentrations (P= 0.755). Tigecycline does not prolong the QTc interval in healthy subjects. This study has been registered at ClinicalTrials.gov under registration no. NCT01287793.

scholarly journals Pharmacokinetics of Benznidazole in Healthy Volunteers and Implications in Future Clinical Trials

2017 ◽  
Vol 61 (4) ◽  
Author(s):  
I. Molina ◽  
F. Salvador ◽  
A. Sánchez-Montalvá ◽  
M. A. Artaza ◽  
R. Moreno ◽  
...  
Keyword(s):  
Chronic Phase ◽  
Volume Of Distribution ◽  
University Hospital ◽  
Pharmacokinetic Parameters ◽  
Triple Quadrupole Mass Spectrometer ◽  
Open Label ◽  
Time Curve ◽  
Drug Of Choice ◽  
Median Volume ◽  
Median Area

ABSTRACT Despite its toxicity and low efficacy in the chronic phase, benznidazole is the drug of choice in Chagas disease. Scarce information about pharmacokinetics and pharmacodynamics of benznidazole has been published. We performed a phase I, open-label, nonrandomized pharmacokinetic study of benznidazole (Abarax) conducted with 8 healthy adult volunteers at the Infectious Diseases Department of the Vall d'Hebron University Hospital (Barcelona, Spain). The separation and detection of benznidazole were performed on a Waters Acquity ultraperformance liquid chromatography system (UPLC) coupled with a Waters Xevo TQ MS triple quadrupole mass spectrometer. The pharmacokinetic parameters were calculated based on a noncompartmental body model using Phoenix WinNonlin version 6.3 software. Furthermore, computational simulations were calculated for the multiple-dose administration at two dose regimens: 100 mg of benznidazole administered every 8 h and 150 mg of benznidazole administered every 12 h. After benznidazole administration, the median area under the concentration-time curve from time zero to time t (AUC0–t ) and extrapolated to infinity (AUC0–∞) were about 46.4 μg · h/ml and 48.4 μg · h/ml, respectively. Plasma benznidazole concentrations peaked at 3.5 h, with maximal concentrations of 2.2 μg/ml, and benznidazole exhibited a terminal half-life of 12.1 h. The median maximum concentration (C max) of benznidazole was lower in men than in women (1.6 versus 2.9 μg/ml), and median volume of distribution (V) as a function of bioavailability (F) was higher in men than in women (125.9 versus 88.6 liters). In conclusion, dose regimens (150 mg/12 h or 100 mg/8 h) reached a steady-state range concentration above of the minimum experimental therapeutic dose. Sex differences in the benznidazole pharmacokinetics were observed; mainly, men had lower C max and higher V/F than women.

scholarly journals Randomized Trial of Food Effect on Pharmacokinetic Parameters of ABX464 Administered Orally to Healthy Male Subjects

2016 ◽  
Vol 61 (1) ◽  
Author(s):  
Didier Scherrer ◽  
Regine Rouzier ◽  
Marine Cardona ◽  
P. Noel Barrett ◽  
Jean-Marc Steens ◽  
...  
Keyword(s):  
Maximum Concentration ◽  
Food Effect ◽  
Randomized Study ◽  
Relative Bioavailability ◽  
Pharmacokinetic Parameters ◽  
Open Label ◽  
Time Curve ◽  
Novel Approach ◽  
Elimination Half ◽  
Group 2

ABSTRACT ABX464 is an antiviral that provides a novel approach to the reduction and control of HIV infection. Investigation of food influence is important in the optimization of treatment. An open-label, food effect, randomized study which included 2 groups of 24 subjects each was carried out to assess the bioavailability and safety of single (group 1) and repeated (group 2) oral doses of ABX464 (50 mg) under fed or fasted conditions. The maximum concentration (C max) and the area under the concentration-time curve from time zero to infinity (AUC0–∞) of ABX464 were demonstrated to increase with food after a single dose of ABX464 (219% and 188%, respectively). The apparent terminal elimination half-lives (t 1/2s) under fed and fasted conditions were comparable, at about 0.80 h. The median time to maximum concentration (T max) was delayed from 1.5 to 2.8 h, and the ratio of the AUC0–∞ obtained under fed conditions to the AUC0–∞ obtained under fasted conditions (F rel) was 2.69. Comparable results were obtained on day 1 and day 10 in group 2. The increases in C max and AUC0–∞ of the metabolite ABX464–N-glucuronide (ABX464-NGlc) were, however, much more limited when ABX464 was given with food. The t 1/2s were also comparable under the two conditions (around 100 h). Between day 1 and day 10, the C max increased by 5% under the fasted condition and by 25% under the fed condition. The most common related treatment-emergent adverse events were headaches, vomiting, and nausea. It was concluded that food has a significant impact on the levels of ABX464 in plasma with a delay in absorption and increased relative bioavailability, with a lesser impact on its biotransformation into ABX464-NGlc. ABX464 was well tolerated under both fasted and fed conditions. (This study has been registered at ClinicalTrials.gov under registration no. NCT02731885.)

scholarly journals Relative oral bioavailability of three formulations of vitamin D3: An open-label, three-treatment study

2018 ◽  
Vol 8 (1) ◽  
pp. 138 ◽  
Author(s):  
Krishnakumar M. Nandgaye ◽  
Rajaram S. Samant ◽  
Santoshi B. Kadam ◽  
Prashant J. Palkar
Keyword(s):  
Single Dose ◽  
Vitamin D3 ◽  
Relative Bioavailability ◽  
Oral Solution ◽  
Pharmacokinetic Parameters ◽  
Vitamin D2 ◽  
Open Label ◽  
Bioequivalence Range ◽  
Optimal Values ◽  
The Mean

Background: Supplementation of vitamin D2 or vitamin D3 is recommended for vitamin D deficiency. Weekly supplementation of 60,000 IU of vitamin D3 increases serum 25(OH) D to optimal values. Various marketed forms of vitamin D3 include tablets, capsule, granules and oral solution. The main objective of this study is to compare the relative bioavailability of vitamin D3 oral solution with vitamin D3 tablet and capsule.Methods: This is an open-label, randomized, single-dose, three-treatment study to compare the relative bioavailability of vitamin D3 oral solution with capsule and tablet. Subjects (n=70) were supplemented with single dose of one of these formulations and their blood sample were assessed for Cmax, AUC0-28d and Tmax.Results: The logarithmic transformed data of pharmacokinetic parameters were analyzed for 90% Confidence Intervals (CI) using ANOVA. The mean (90% CI) values of vitamin D3 oral solution against tablet for the ratio of Cmax and AUC0-28d were 113.00 (105.32-121.23) and 105.54 (97.95-113.72) respectively. The mean (90% CI) values of vitamin D3 oral solution against capsule for the ratio of Cmax and AUC0-28d were 115.02 (106.38 - 124.37) and 112.33 (104.44 - 120.81) respectively. These values were within the bioequivalence range of 80-125%.Conclusions: It is concluded that vitamin D3 Oral Solution formulated with nanotechnology is bioequivalent to vitamin D3 tablet and capsule. However, oral solution of vitamin D3 shows higher Cmax and AUC when compared to tablet and capsule formulations.

scholarly journals The relative bioavailability of two formulations containing 10 mg Dapagliflozin assessed under fasting conditions in a randomized crossover study in healthy Caucasian subjects

2020 ◽  
Vol 66 (1) ◽  
pp. 30-34
Author(s):  
Monica Oroian ◽  
Diana Ioana Pop ◽  
Ana-Maria Gheldiu ◽  
Sandeep Bhardwaj ◽  
Adriana Marcovici ◽  
...  
Keyword(s):  
Single Dose ◽  
Reference Product ◽  
Area Under The Curve ◽  
Immediate Release ◽  
Relative Bioavailability ◽  
Pharmacokinetic Analysis ◽  
Pharmacokinetic Parameters ◽  
Maximum Plasma ◽  
Open Label ◽  
Pharmaceutical Industries

AbstractObjective: The aim of the present study was to evaluate the relative bioavailability of two formulations containing 10 mg dapagliflozin in healthy Caucasian subjects under fasting conditions.Materials and Methods: Forty-eight healthy Caucasian subjects were enrolled in a single-dose, crossover, balanced, open label, randomized clinical trial, with two treatment, two periods and two sequences. The wash-out period was of 7 days and thirty-eight subjects completed both study periods. Each subject received a single dose of 10 mg dapagliflozin as the reference product Farxiga® (AstraZeneca Pharmaceuticals LP, USA) and the test product developed by Sun Pharmaceutical Industries, India. Dapagliflozin plasma levels were determined from blood samples collected in both study periods before and after dosing until 48 hours by using a validated LC-MS/MS method. For pharmacokinetic analysis of data, the non-compartmental method was used (Phoenix® WinNonlin 6.3). The statistical analysis was performed by SAS software 9.1.3 for the logarithmically transformed values of maximum plasma concentration and area under the curve.Results: The 90% confidence intervals for the evaluated pharmacokinetic parameters were found to be in the accepted interval for bioequivalence (80.00-125.00%).Conclusion: The 10 mg dapagliflozin immediate release tablet newly developed by Sun Pharmaceutical Industries, India, is bioequivalent with the reference product Farxiga® under fasted state of the subjects.

scholarly journals Pharmacokinetics and Bioequivalence of Isavuconazole Administered as Isavuconazonium Sulfate Intravenous Solution via Nasogastric Tube or Orally in Healthy Subjects

2021 ◽  
Author(s):  
Amit Desai ◽  
Melanie Helmick ◽  
Nakyo Hoe ◽  
Selina Moy ◽  
Stephen Stanhope ◽  
...  
Keyword(s):  
Single Dose ◽  
Oral Administration ◽  
Fungal Infections ◽  
Open Label ◽  
Serious Adverse Events ◽  
Time Curve ◽  
Mean Values ◽  
Routes Of Administration ◽  
Period 2 ◽  
Intravenous Solution

For critically ill patients with invasive fungal infections, administration of isavuconazonium sulfate (ISAVUSULF) via nasogastric (NG) tube can be an alternative route of drug administration. This was a randomized, open-label, 2-period, 2-sequence single-dose crossover study comparing single doses of 372 mg ISAVUSULF intravenous (IV) solution via NG tube (test formulation) to 372 mg ISAVUSULF capsules for oral administration (reference formulation) in healthy male and female subjects. A single dose of ISAVUSULF was administered under fasting conditions on Day 1 of each period, with a washout of 30 days between each period. Pharmacokinetic (PK) samples were collected predose through Day 21. Standard safety and tolerability assessments were conducted in each period. The analysis of variance estimate of the study population demonstrates that the isavuconazole IV NG tube administration Geometric least squares (LS) mean values of the observed maximum concentration (C max ), area under the plasma concentration–time curve (AUC) to the last measurable concentration (AUC last ), AUC to time infinity (AUC inf ), and AUC from start of dosing to 72 hours (AUC 72 ) were 105.3%, 97.6%, 99.3% and 97.8%, respectively, of the corresponding oral administration values. The Geometric LS mean ratio and 90% confidence intervals for the PK parameters were completely contained within the prespecified limits of 80% to 125%. There were no deaths or serious adverse events that led to the withdrawal of treatment during the study. The study met its primary endpoint of bioequivalence between the two routes of administration. Both routes of administration were well tolerated.

scholarly journals Pharmacokinetics and Bioequivalence Study of Two Ciprofloxacin Hydrochloride Tablets in Chinese Healthy Volunteers Under Fasting and Fed Conditions: A Randomized, Open-Label, Two-Formulation, Two-Sequence, Two-Period, Single-Dose Crossover Study.

2020 ◽  
Author(s):  
Fei Qin ◽  
Gan-Mi Wang ◽  
Jin-Ying Huang ◽  
Jia-Rong Wu ◽  
Wen-Jie Song ◽  
...  
Keyword(s):  
Single Dose ◽  
Plasma Concentration ◽  
Oral Dose ◽  
Single Oral Dose ◽  
Pharmacokinetic Parameters ◽  
Open Label ◽  
Time Curve ◽  
Ciprofloxacin Hydrochloride ◽  
Concentration Time ◽  
Plasma Concentration Time Curve

Abstract BackgroundCiprofloxacin is a broad-spectrum fluoroquinolone antibiotic which is active against a wide range of Gram-positive and Gram-negative bacteria. The study mainly aimed to determine the bioequivalence of two branded ciprofloxacin hydrochloride tablets (250 mg) under the fasting and fed conditions.MethodsThe study was carried out in 48 healthy Chinese subjects under fasting and fed conditions with a randomized, open-label, two-formulation, two-sequence, two-period, single-dose crossover design. In each period of the study, the subjects were assigned to receive a single oral dose of 250 mg of ciprofloxacin hydrochloride. Blood samples were collected from an hour before dosing to 36 h after administration with 16 time points in total. The bioequivalence analysis was performed after ln-transformation of the ciprofloxacin pharmacokinetic parameters including maximum concentration (Cmax), area under the plasma concentration–time curve from time 0 to time t (AUC0-t), area under the plasma concentration-time curve from time 0 to infinity (AUC0-∞). Two formulations are considered bioequivalent if the 90% confidence intervals (CIs) for the test/reference geometric mean ratios (GMRs) for the ln-transformed pharmacokinetic parameters fall within the standard acceptance range of 80% – 125%. ResultsIn total of 48 subjects were enrolled in the fasting and fed studies, and one of the subjects was excluded before the administration. In the fasting study, the 90% CIs for the test/reference GMRs of the ln-transformed data for Cmax, AUC0–t, and AUC0–∞ were 85.41% to 100.97%, 95.40% to 100.27%, and 95.48% to 100.30%, respectively. For the fed study, the 90% CIs for the test/reference GMRs of the ln-transformed data for Cmax, AUC0–t, and AUC0–∞ were 90.15% to 113.75%, 99.10% to 103.77% and 99.11% to 103.80%, respectively. A total of 8 of 47 subjects experienced AEs in the fasting and fed studies.ConclusionsIn the study, the generic (test) product of ciprofloxacin hydrochloride 250 mg was bioequivalent to the innovator (reference) product after a single oral dose administration under the fasting and fed conditions. Both two brands of ciprofloxacin tablets were safe and well tolerated.Trial registrationThe clinical trial was registered at Center for the Drug Evaluation of the National Medical Products Administration (registration number: CTR20171152; date of registration：September 25, 2017; http://www.chinadrugtrials.org.cn/clinicaltrials.searchlistdetail.dhtml).

Lack of Effect of Ginkgo biloba on Voriconazole Pharmacokinetics in Chinese Volunteers Identified as CYP2C19 Poor and Extensive Metabolizers

2009 ◽  
Vol 43 (4) ◽  
pp. 726-731 ◽  
Author(s):  
He-Ping Lei ◽  
Guo Wang ◽  
Lian-Sheng Wang ◽  
Dong-sheng Ou-yang ◽  
Hao Chen ◽  
...  
Keyword(s):  
Single Dose ◽  
Ginkgo Biloba ◽  
Poor Metabolizers ◽  
Pharmacokinetic Parameters ◽  
Extensive Metabolizers ◽  
Herbal Supplements ◽  
Time Curve ◽  
Concentration Time ◽  
Apparent Clearance ◽  
Randomized Crossover Study

Background: Ginkgo biloba is one of the most popular herbal supplements in the world. The supplement has been shown to induce the enzymatic activity of CYP2C19, the main cytochrome P450 isozyme involved in voriconazole metabolism. Because this enzyme exhibits genetic polymorphism, the inductive effect was expected to be modulated by the CYP2C19 metabolizer status. Objective: To examine the possible effects of Ginkgo biloba as an inducer of CYP2C19 on single-dose pharmacokinetics of voriconazole in Chinese volunteers genotyped as either CVP2C19 extensive or poor metabolizers. Methods: Fourteen healthy, nonsmoking volunteers–7 CYP2C19 extensive metabolizers (2C19*1/2C19*1) and 7 poor metabolizers (2C19*2/2C19*2)–were selected to participate in this study. Pharmacokinetics of oral voriconazole 200 mg after administration of Ginkgo biloba 120 mg twice daily for 12 days were determined for up to 24 hours by liquid chromatography–electrospray tandem mass spectrometry in a 2-phase randomized crossover study with 4-week washout between phases. Results: For extensive metabolizers, the median value for voriconazole area under the plasma concentration–time curve from zero to infinity (AUC0-00) was 5.17 μg•h/mL after administration of voriconazole alone and 4.28 μg•/mL after voriconazole with Ginkgo biloba (p > 0.05). The other pharmacokinetic parameters of voriconazole such as AUC0-24, time to reach maximum concentration, half-life, and apparent clearance also did not change significantly for extensive metabolizers in the presence of Ginkgo biloba. Pharmacokinetic parameters followed a similar pattern for poor metabolizers. Conclusions: The results suggest that 12 days of treatment with Ginkgo biloba did not significantly alter the single-dose pharmacokinetics of voriconazole in either CYP2C19 extensive or poor metabolizers. Therefore, the pharmacokinetic interactions between voriconazole and Ginkgo biloba may have limited clinical significance.

Sign in / Sign up

Export Citation Format

Share Document