scholarly journals Effect of H2Blockade and Food on Single-Dose Pharmacokinetics of GSK1322322, a Peptide Deformylase Inhibitor Antibacterial

2013 ◽  
Vol 57 (6) ◽  
pp. 2556-2561 ◽  
Author(s):  
Odin J. Naderer ◽  
Etienne Dumont ◽  
John Zhu ◽  
Milena Kurtinecz ◽  
Lori S. Jones
Keyword(s):  
Single Dose ◽  
Plasma Concentration ◽  
Vitamin C ◽  
Relative Bioavailability ◽  
Peptide Deformylase ◽  
Maximum Plasma ◽  
High Fat ◽  
Tablet Formulations ◽  
Fast Release ◽  
Fat Meal

ABSTRACTGSK1322322 is first in a new class of antibiotics, peptide deformylase inhibitors, and is active against multidrug-resistant respiratory and skin pathogens. Part 1 of this phase 1, randomized, single-dose (1,000 mg) study in 20 healthy volunteers compared the relative bioavailability of three different tablet formulations of GSK1322322 (fast release, intermediate release, and slow release) to that of the previously studied powder-in-bottle formulation to assess the optimal formulation for progression into clinical trials. Part 2 assessed the effect of a high-fat meal and drug interaction with an H2blocker and an H2blocker plus vitamin C on the pharmacokinetic profile of GSK1322322. Of the three tablet formulations, fast-release GSK1322322 provided pharmacokinetic profiles similar to those of the powder-in-bottle reference formulation (∼93% relative bioavailability) and was selected for progression in part 2. When GSK1322322 was administered with a high-fat meal, the maximum observed plasma concentration (Cmax) was reduced by 20%, and the time to maximum plasma concentration (Tmax) was delayed by 1.9 h. The exposure (area under the concentration-time curve [AUC]) increased by ∼20% compared to that in volunteers in the fasted state. Coadministration of GSK1322322 with an H2blocker resulted in a slight delay in absorption (Tmax∼0.75 h later) and 58 and 38% decreases in theCmaxand AUC0–∞values, respectively, compared to GSK1322322 alone. This effect was reversed with vitamin C intake (i.e., no delay inTmaxand theCmaxand AUC0–∞values decreased by only 21 and 12%, respectively). GSK1322322 was generally well tolerated, and most adverse events were mild in intensity during both parts of the study.

scholarly journals Single-Dose Safety, Tolerability, and Pharmacokinetics of the Antibiotic GSK1322322, a Novel Peptide Deformylase Inhibitor

2013 ◽  
Vol 57 (5) ◽  
pp. 2005-2009 ◽  
Author(s):  
Odin J. Naderer ◽  
Etienne Dumont ◽  
John Zhu ◽  
Milena Kurtinecz ◽  
Lori S. Jones
Keyword(s):  
Single Dose ◽  
Plasma Concentration ◽  
Dose Escalation ◽  
Peptide Deformylase ◽  
Maximum Plasma ◽  
High Fat ◽  
Content Type ◽  
Atypical Pathogens ◽  
Fat Meal ◽  
Dose Proportional

ABSTRACTGSK1322322 is a potent inhibitor of peptide deformylase, an essential bacterial enzyme required for protein maturation. GSK1322322 is active against community-acquired skin and respiratory tract pathogens, including methicillin-resistantStaphylococcus aureus, multidrug-resistantStreptococcus pneumoniae, and atypical pathogens. This phase I, randomized, double-blind, placebo-controlled, 2-part, single-dose, dose escalation study (first time in humans) evaluated the safety, tolerability, and pharmacokinetics of GSK1322322 (powder-in-bottle formulation) in healthy volunteers. In part A, dose escalation included GSK1322322 doses of 100, 200, 400, 800, and 1,500 mg under fasting conditions and 800 mg administered with a high-fat meal. In part B, higher doses of GSK1322322 (2,000, 3,000, and 4,000 mg) were evaluated under fasting conditions. Of the 39 volunteers enrolled in the study, 29 and 10 volunteers were treated with GSK1322322 and placebo, respectively. Upon single-dose administration, GSK1322322 was absorbed rapidly, with median times to maximum plasma concentration (Tmax) ranging from 0.5 to 1.0 h. The maximum observed plasma concentration (Cmax) and exposure (area under the concentration-time curve [AUC]) of GSK1322322 were greater than dose proportional between 100 and 1,500 mg and less than dose proportional between 1,500 and 4,000 mg. Administration of the drug with a high-fat meal reduced the rate of absorption (reducedCmaxand delayedTmax) without affecting the extent of absorption (no effect on AUC). GSK1322322 was generally well tolerated, with all adverse events being mild to moderate in intensity during both parts of the study. The most frequently reported adverse event was headache. Data from this study support further evaluation of GSK1322322.

Bioavailability of Three Commercial Preparations of Ibuprofen 600 mg

1988 ◽  
Vol 16 (1) ◽  
pp. 44-49 ◽  
Author(s):  
E. Källström ◽  
M. Heikinheimo ◽  
H. Quiding
Keyword(s):  
Single Dose ◽  
Plasma Concentration ◽  
Crossover Study ◽  
Healthy Volunteers ◽  
Plasma Concentrations ◽  
Analgesic Efficacy ◽  
Relative Bioavailability ◽  
Maximum Plasma ◽  
The Mean ◽  
Extent Of Absorption

The pharmacokinetic variables of ibuprofen 600 mg were investigated after administration of Brufen and compared to administration of Burana and Ibumetin. The investigation was carried out as a randomized single-dose crossover study in 17 healthy volunteers. The mean maximum plasma concentrations of ibuprofen were 58, 45 and 54 μg/ml after administration of Brufen, Burana and Ibumetin, respectively, the time to reach this being 1.4, 2.1 and 1.6 h, respectively, after administration. The differences between Brufen and Burana were significant. The relative bioavailability was very similar between Brufen and Burana but about 8% lower for Ibumetin and this difference between Brufen and Ibumetin was significant. Thus, different brands of ibuprofen may not be pharmacokinetically interchangeable and the results show that Brufen is superior to either Burana or Ibumetin when considering both the rate and extent of absorption. These findings are clinically interesting since a high and early plasma concentration of ibuprofen seems to be related to increased analgesic efficacy.

scholarly journals Pharmacokinetics and Biodistribution of Zinc-Enriched Yeast in Rats

2014 ◽  
Vol 2014 ◽  
pp. 1-4 ◽  
Author(s):  
Shuangqing Zhang ◽  
Yan Zhang ◽  
Ning Peng ◽  
Haibo Zhang ◽  
Juan Yao ◽  
...  
Keyword(s):  
Single Dose ◽  
Plasma Concentration ◽  
Inductively Coupled Plasma ◽  
Zinc Sulfate ◽  
Optical Emission ◽  
Relative Bioavailability ◽  
Emission Spectrometry ◽  
Maximum Plasma ◽  
Inductively Coupled ◽  
Plasma Optical Emission Spectrometry

Zinc-enriched yeast (ZnY) and zinc sulfate (ZnSO4) are considered zinc (Zn) supplements currently available. The purpose of the investigation was to compare and evaluate pharmacokinetics and biodistribution of ZnY and ZnSO4in rats. ZnY or ZnSO4were orally administered to rats at a single dose of 4 mg Zn/kg and Zn levels in plasma and various tissues were determined using inductively coupled plasma-optical emission spectrometry. Maximum plasma concentration values were 3.87 and 2.81 μg/mL for ZnY and ZnSO4, respectively. Both ZnY and ZnSO4were slowly eliminated with a half-life of over 7 h and bone had the highest Zn level in all tissues. Compared to ZnSO4, the relative bioavailability of ZnY was 138.4%, indicating that ZnY had a significantly higher bioavailability than ZnSO4.

Effect of a high-fat meal on the relative bioavailability of H3B-6527, a novel FGFR4 inhibitor, in healthy volunteers

2018 ◽  
Vol 83 (1) ◽  
pp. 91-96 ◽  
Author(s):  
Nathalie Rioux ◽  
Amy Kim ◽  
Darrell Nix ◽  
Todd Bowser ◽  
Markus Warmuth ◽  
...  
Keyword(s):  
Healthy Volunteers ◽  
Relative Bioavailability ◽  
High Fat ◽  
Fat Meal

Effect of a high-fat meal on thalidomide pharmacokinetics and the relative bioavailability of oral formulations in healthy men and women

2000 ◽  
Vol 21 (1) ◽  
pp. 33-40 ◽  
Author(s):  
Steve K. Teo ◽  
Michael R. Scheffler ◽  
Karin A. Kook ◽  
William G. Tracewell ◽  
Wayne A. Colburn ◽  
...  
Keyword(s):  
Relative Bioavailability ◽  
High Fat ◽  
Men And Women ◽  
Healthy Men ◽  
Oral Formulations ◽  
Fat Meal

scholarly journals A Novel Amorphous Curcumin Preparation Improved Oral Absorption Efficiency in Healthy Volunteers: A Single-Dose, Double-Blind, Two-Way Crossover Study

2020 ◽  
Author(s):  
Yoichi Sunagawa ◽  
Yusuke Miyazaki ◽  
Masafumi Funamoto ◽  
Kana Shimizu ◽  
Satoshi Shimizu ◽  
...  
Keyword(s):  
Single Dose ◽  
Plasma Concentration ◽  
Crossover Study ◽  
Healthy Volunteers ◽  
Oral Absorption ◽  
Biological Activities ◽  
Absorption Efficiency ◽  
Amorphous Solid Dispersion ◽  
Maximum Plasma ◽  
Double Blind

Abstract Background: Curcumin has diverse biological activities such as anti-cancer, antioxidant, and anti-inflammatory properties and is assumed to exhibit beneficial effects in the prevention and treatment of various diseases. Although curcumin is known to be safe in humans, its therapeutic efficacy is limited owing to its poor bioavailability. To overcome this problem, we prepared a novel curcumin preparation curcuRougeTM using the amorphous solid dispersion method. In this study, we aimed to investigate the oral absorption efficiency of curcuRougeTM and compare its efficiency with that of Theracurmin®, a highly absorptive curcumin preparation dispersed with colloidal submicron-particles exhibiting improved bioavailability, in rats and healthy volunteers. Methods: In the animal experiment, male Sprague–Dawley rats were orally administered curcuRougeTM or Theracurmin® (10 mg/kg of curcumin). The plasma curcumin levels were measured at 0.25, 0.5, 1, 2, 4, and 6 h after administration. In addition, we performed a single-dose, double-blind, two-way crossover study to compare plasma curcumin levels after the administration of curcuRougeTM or Theracurmin® in humans. Twelve healthy volunteers were administered curcuRougeTM or Theracurmin® containing 30 mg curcumin. The plasma curcumin concentrations at 0.5, 1, 2, 4, and 8 h after ingestion were determined. Results: The area under plasma concentration–time curve (AUC0-6 h) and maximum plasma concentration (Cmax) of curcuRougeTM in rats were 3.7- and 9.6-fold higher than those of Theracurmin®, respectively. Twelve healthy volunteers were orally administered 90 mg of curcuRougeTM or Theracurmin® in a randomized double-blind crossover study. In these volunteers, the AUC0-8 h and Cmax of curcuRougeTM were 3.4-fold and 5.4-fold higher than those of Theracurmin®, respectively. Conclusion: These findings indicate that curcuRougeTM shows better bioavailability than other highly absorptive curcumin preparations, such as Theracurmin®. Hence, curcuRougeTM is assumed to exhibit clinical efficacy for managing various diseases at a low dose.Trial registration: The trial was registered with the UMIN Clinical Trials Registry (January 8, 2020, UMIN000039083, https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000044573).

scholarly journals Bioequivalence of levamlodipine besylate tablets in healthy Chinese subjects: A single-dose and two-period crossover randomized study

2020 ◽  
Author(s):  
Li Xin ◽  
Chenjing Wang ◽  
Ting Li ◽  
Yanping Liu ◽  
Shuqin Liu ◽  
...  
Keyword(s):  
Single Dose ◽  
Randomized Study ◽  
Pharmacokinetic Parameters ◽  
Reference Formulation ◽  
High Fat ◽  
Fasting Condition ◽  
Test Formulation ◽  
Healthy Chinese ◽  
Chinese Subjects ◽  
Fat Meal

Abstract Background: Levamlodipine, a calcium channel blocker, is used in treatment of hypertension. To compare the pharmacokinetic parameters between levamlodipine test formulation at a single dose of 5 mg and amlodipine reference formulation at a single dose of 10 mg, the bioequivalence study was carried out.Methods: A single-dose randomized, open-label, two-period crossover study was designed in healthy Chinese subjects. 48 subjects were divided into fasting and high-fat meal group equally. The subjects randomly received the test or reference formulations at the rate of 1:1. Following a 21-day washout period, the alternative formulations were received. The blood samples were collected at 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 14, 24, 36, 48, 72, 96, 120, 144, 168 hours later. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) was applied to determine levamlodipine in the plasma samples.Results: Within equivalence limits between 80 ~ 125%, the test formulation and the reference formulation were bioequivalent, with the 90% confidence intervals (CIs) for the ratio of geometric means of Cmax, AUC0-t, and AUC0-∞. The data were shown as Cmax (89.59% ~ 101.61%), AUC0-t (87.83% ~ 94.87%) and AUC0-∞ (86.28% ~ 93.49%) under fasting condition, Cmax (90.93% ~ 102.37%), AUC0–t (95.75% ~ 104.93%) and AUC0–∞ (95.36% ~ 105.33%) under high-fat meal condition. Serious adverse event was not observed.Conclusions: The trial confirmed that levamlodipine at a single dose of 5 mg and amlodipine at a single dose of 10 mg were bioequivalent under both fasting condition and high-fat meal condition.Trial registration: Cinicaltrials, NCT04411875. Registered 3 June 2020 - Retrospectively registered, https://register.clinicaltrials.gov/prs/app/action/SelectProtocol?sid=S0009W1Q&selectaction=Edit&uid=U00050YQ&ts=3&cx=-6iqkm8

scholarly journals Single-Dose Phase I Study To Evaluate the Pharmacokinetics of Posaconazole in New Tablet and Capsule Formulations Relative to Oral Suspension

2012 ◽  
Vol 56 (8) ◽  
pp. 4196-4201 ◽  
Author(s):  
Gopal Krishna ◽  
Lei Ma ◽  
Monika Martinho ◽  
Edward O'Mara
Keyword(s):  
Single Dose ◽  
Phase I ◽  
Coefficient Of Variation ◽  
Phase I Study ◽  
Area Under The Curve ◽  
Oral Suspension ◽  
High Fat ◽  
Open Label ◽  
Proven Efficacy ◽  
Fat Meal

ABSTRACTPosaconazole oral suspension, a marketed extended-spectrum triazole with proven efficacy as antifungal treatment and prophylaxis, should be taken with food to maximize absorption. New tablet and capsule formulations have been developed in an attempt to optimize absorption and bioavailability. The aims of this exploratory open-label, partially randomized, 2-part, 4-way, single-dose crossover study in 16 healthy adults were to characterize pharmacokinetics for posaconazole tablet and capsule formulations relative to those for posaconazole oral suspension under fasted and fed conditions and to assess safety and tolerability. Under fasted conditions, posaconazole exposures (area under the curve [AUC]) for the tablet and capsule formulations were similar (mean AUC from time zero to infinity [AUC0–∞], tablet A, 11,700 ng · h/ml [coefficient of variation {CV}, 26%]; tablet B, 11,300 ng · h/ml [CV, 22%]; capsule, 11,000 ng · h/ml [CV, 25%]) and were substantially higher than the exposure for the oral suspension (mean AUC0–∞, 3,420 ng · h/ml [CV, 44%]). Tablets and capsule showed less variability in exposure than the oral suspension. In fed subjects, tablets and capsule resulted in similar AUC values (mean AUC0–∞, tablet A, 11,900 ng · h/ml [23%]; tablet B, 12,400 ng · h/ml [CV, 25%]; capsule, 12,300 ng · h/ml [CV, 28%]) and slightly higher exposure than the oral suspension (mean AUC0–∞, 8,750 [CV, 24%]). Median times to the maximum concentration of drug in plasma were 4 to 5 h (fasted conditions) and 6 to 8 h (fed conditions). Mean half-lives values were similar for all formulations under fed and fasted conditions (23.1 to 29.2 h). Consistent with previous data, exposure for the oral suspension increased 2.5- to 3-fold when it was given with a high-fat meal. Conversely, exposures for tablets and capsule were not markedly affected by food. All formulations of posaconazole at 100 mg were safe and well tolerated.

Sign in / Sign up

Export Citation Format

Share Document