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 Comparative Pharmacokinetics of Azithromycin in Serum and White Blood Cells of Healthy Subjects Receiving a Single-Dose Extended-Release Regimen versus a 3-Day Immediate-Release Regimen

2006 ◽  
Vol 51 (1) ◽  
pp. 103-109 ◽  
Author(s):  
Ping Liu ◽  
Hameed Allaudeen ◽  
Richa Chandra ◽  
Kem Phillips ◽  
Arvid Jungnik ◽  
...  
Keyword(s):  
Single Dose ◽  
Blood Cells ◽  
Dose Regimen ◽  
Extended Release ◽  
Drug Exposure ◽  
White Blood Cells ◽  
Area Under The Curve ◽  
Immediate Release ◽  
Mononuclear Leukocytes ◽  
Open Label

ABSTRACT The pharmacokinetic profiles of azithromycin given as a single-dose regimen (2.0-g extended-release microspheres) were characterized in serum and white blood cells (WBC) and compared with those of a 3-day regimen (a 500-mg immediate-release tablet once daily; total dose, 1.5 g) in an open-label, randomized, parallel-group study of 24 healthy adult subjects. Serial blood samples were collected up to 5 days after the start of dosing for both regimens. Safety assessments were conducted throughout the study. A single 2.0-g dose of azithromycin microspheres achieved significantly higher exposures in serum and WBC during the first 24 h after the start of dosing than a 3-day regimen: an approximately threefold higher area under the curve from time zero to 24 h postdose (AUC0-24) and an approximately twofold higher mean peak concentration on day 1. The single-dose regimen provided total azithromycin exposures in serum and WBC similar to those of the 3-day regimen, as evidenced by the similar AUC0-120 and trough azithromycin concentrations in serum and WBC (mononuclear leukocytes [MNL] and polymorphonuclear leukocytes [PMNL]). For both regimens, the average total azithromycin exposures in MNL and PMNL were approximately 300- and 600-fold higher than those in serum. Azithromycin concentrations in MNL and PMNL remained above 10 μg/ml for at least 5 days after the start of dosing for both regimens. This “front-loading” of the dose on day 1 is safely achieved by the extended-release microsphere formulation, which maximizes the drug exposure at the time when the bacterial burden is likely to be highest.

scholarly journals Injectable Dexamethasone Sodium Phosphate Administered Orally? A Pharmacokinetic Analysis of a Common Emergency Department Practice

2015 ◽  
Vol 20 (2) ◽  
pp. 105-111
Author(s):  
Alexander Toledo ◽  
Christopher S. Amato ◽  
Nigel Clarke ◽  
Richard E. Reitz ◽  
David Salo
Keyword(s):  
Sodium Phosphate ◽  
Area Under The Curve ◽  
Relative Bioavailability ◽  
Healthy Adults ◽  
Absolute Bioavailability ◽  
Pharmacokinetic Analysis ◽  
Pharmacokinetic Data ◽  
Open Label ◽  
Dexamethasone Sodium Phosphate ◽  
The Mean

BACKGROUND: The injectable formulation of dexamethasone has been administered orally, for the treatment of pediatric asthma and croup. The practice is followed in emergency departments around the country, but pharmacokinetic data supporting this practice are lacking. OBJECTIVES: This study evaluated the relative bioavailability and pharmacokinetics of dexamethasone sodium phosphate for injection (DSPI) administered orally compared to dexamethasone oral concentrate (DOC) in healthy adults. METHODS: This was an open label, crossover study of 11 healthy adults 18 to 45 years of age. All subjects received 8 mg of dexamethasone oral concentrate initially. After a 1-week wash-out period, subjects received 8 mg of DSPI administered orally. Dexamethasone levels were measured by liquid chromatography in tandem mass spectrometry. Cmax and area under the curve (AUC (0-t) and AUC (0-∞)) were calculated and compared between groups using the paired t test. RESULTS: The mean ± SD AUC(0-t) for dexamethasone oral concentrate and DSPI were 5497.23 ± 1649 and 4807.82 ± 1971) ng/dL/hr, respectively; 90% confidence interval (CI) was 78.8%–96.9%. The mean ± SD AUC(0-∞) for dexamethasone oral concentrate and DSPI were 6136.43 ± 2577 and 5591.48 ± 3075 ng/dL/hr, respectively; 90% CI was 79.0% –105.2%. Mean Cmax ± SD for DOC and DSPI were 942.94 ± 151 and 790.92 ± 229 ng/dL, respectively; 90% CI 76.8%–91.7%. The relative bioavailability of DSPI administered orally was 87.4% when using AUC(0-t) and 91.1% when using AUC(0-∞). The calculated absolute bioavailability was 75.9%. CONCLUSIONS: DSPI is not bioequivalent to dexamethasone oral concentrate when administered orally. The existing literature supports the efficacy of DSPI despite this. Dosing adjustments may be considered.

scholarly journals Drug-Drug Interaction between the Direct-Acting Antiviral Regimen of Ombitasvir-Paritaprevir-Ritonavir plus Dasabuvir and the HIV Antiretroviral Agent Dolutegravir or Abacavir plus Lamivudine

2016 ◽  
Vol 60 (10) ◽  
pp. 6244-6251 ◽  
Author(s):  
Amit Khatri ◽  
Roger Trinh ◽  
Weihan Zhao ◽  
Thomas Podsadecki ◽  
Rajeev Menon
Keyword(s):  
Geometric Mean ◽  
Area Under The Curve ◽  
Pharmacokinetic Parameters ◽  
Maximum Plasma ◽  
Virus Genotype ◽  
Open Label ◽  
Direct Acting Antiviral ◽  
Central Value ◽  
Dose Study ◽  
Direct Acting

ABSTRACTThe direct-acting antiviral regimen of 25 mg ombitasvir–150 mg paritaprevir–100 mg ritonavir once daily (QD) plus 250 mg dasabuvir twice daily (BID) is approved for the treatment of hepatitis C virus genotype 1 infection, including patients coinfected with human immunodeficiency virus. This study was performed to evaluate the pharmacokinetic, safety, and tolerability effects of coadministering the regimen of 3 direct-acting antivirals with two antiretroviral therapies (dolutegravir or abacavir plus lamivudine). Healthy volunteers (n= 24) enrolled in this phase I, single-center, open-label, multiple-dose study received 50 mg dolutegravir QD for 7 days or 300 mg abacavir plus 300 mg lamivudine QD for 4 days, the 3-direct-acting-antiviral regimen for 14 days, followed by the 3-direct-acting-antiviral regimen with dolutegravir or abacavir plus lamivudine for 10 days. Pharmacokinetic parameters were calculated to compare combination therapy with 3-direct-acting-antiviral or antiretroviral therapy alone, and safety/tolerability were assessed throughout the study. Coadministration of the 3-direct-acting-antiviral regimen increased the geometric mean maximum plasma concentration (Cmax) and the area under the curve (AUC) of dolutegravir by 22% (central value ratio [90% confidence intervals], 1.219 [1.153, 1.288]) and 38% (1.380 [1.295, 1.469]), respectively. Abacavir geometric meanCmaxand AUC values decreased by 13% (0.873 [0.777, 0.979]) and 6% (0.943 [0.901, 0.986]), while those for lamivudine decreased by 22% (0.778 [0.719, 0.842]) and 12% (0.876 [0.821, 0.934]). For the 3-direct-acting-antiviral regimen, geometric meanCmaxand AUC during coadministration were within 18% of measurements made during administration of the 3-direct-acting-antiviral regimen alone, although trough concentrations for paritaprevir were 34% (0.664 [0.585, 0.754]) and 27% (0.729 [0.627, 0.847]) lower with dolutegravir and abacavir-lamivudine, respectively. All study treatments were generally well tolerated, with no evidence of increased rates of adverse events during combination administration. These data indicate that the 3-direct-acting-antiviral regimen can be administered with dolutegravir or abacavir plus lamivudine without dose adjustment.

scholarly journals The Statistical Analysis of Pharmacokinetic Parameters in the Context of Bioequivalence Testing of Two Anthelmintic Formulas Based on Ivermectine and Triclabendazole in Sheep

2019 ◽  
Vol 65 (2) ◽  
pp. 60-65
Author(s):  
Lenard Farczadi ◽  
Laurian Vlase ◽  
Orsolya Melles ◽  
Ramona Tolomeiu ◽  
Octavia Tamas-Krumpe ◽  
...  
Keyword(s):  
High Performance ◽  
Reference Product ◽  
Plasma Concentrations ◽  
Pharmaceutical Formulations ◽  
Relative Bioavailability ◽  
Pharmacokinetic Analysis ◽  
Pharmacokinetic Parameters ◽  
Pharmacokinetic Data ◽  
Test Product

AbstractConducting bioequivalence studies is an essential step during the market authorization process of generic pharmaceutical formulations, for both human or veterinary use. The aim of the present study was to evaluate the pharmacokinetics of triclabendazole sulphoxide, the main metabolite of triclabendazole, and ivermectin in order to evaluate the bioavailability and bioequivalence of a novel sheep anthelmintic formulation of oral suspension for sheep treatment containing triclabendazole 50 mg/mL and ivermectin 1 mg/mL compared to the reference product. In order to determine relative bioavailability of the test product with respect to the reference product the study was conducted on 36 clinically healthy sheep, following an unicentric, randomized, cross-over, two-sequence, two-treatment and 14-day wash-out study design. For the determination of triclabendazole sulphoxide and ivermectin sheep plasma concentrations, two rapid, selective high performance liquid chromatography coupled with mass spectrometry (LC-MS/MS) methods were developed and validated. The measured plasma concentrations of triclabendazole sulphoxide and ivermectin were used for the pharmacokinetic analysis and the determination of bioequivalence between the test product with regards to the reference product. The noncompartmental analysis of the pharmacokinetic data for both triclabendazole sulphoxide and ivermectin showed similarities between first-order kinetics of the test and reference product. The relevant pharmacokinetic parameters (Cmax, AUClast, AUCtot) were determined and the bioequivalence between the test and reference product could be concluded.

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.

scholarly journals A comparative pharmacokinetics study of Ashwagandha (Withania somnifera) Root Extract sustained-release capsules: an open-label, randomized, two treatment, two-sequence, two period, single-dose crossover clinical study

2021 ◽  
Author(s):  
Venkata Krishna Raju Alluri ◽  
Shefali Thanawala ◽  
Vivek Upadhyay
Keyword(s):  
Single Dose ◽  
Sustained Release ◽  
Withania Somnifera ◽  
Reference Product ◽  
Relative Bioavailability ◽  
Release Profile ◽  
Root Extract ◽  
Open Label ◽  
Test Product ◽  
Withanolide A

Background: In this open-label, randomized, balanced, two-treatment, two-sequence, two-period, crossover, single-dose oral comparative pharmacokinetics study, the pharmacokinetics, safety, and tolerability of test product ‘ashwagandha (Withania somnifera)’ root extract sustained release capsule 300 mg (Prolanza™), each containing 15 mg withanolides (administered dose: 2×15 mg) was compared with that of a reference product (organic KSM-66 ashwagandha extract [vegan] capsule, each containing 15 mg withanolides [administered dose: 2×15 mg]).Methods: Total 14 healthy men were randomized to receive either the test or the reference product as a single dose of 2 capsules in sequence, administered under fasting conditions. Plasma concentrations of total withanolides, withanolide A and 12-deoxywithastramonolide were measured using validated liquid chromatography–mass spectroscopy/mass spectroscopy.Results: The test product had higher relative absorption, better relative bioavailability, and longer elimination half-life indicating a sustained-release profile compared to reference. Specifically, the relative bioavailability of the test formulation was 12, 44, and 11 times higher for total withanolides, withanolide A and 12-deoxywithastramonolide, respectively. No adverse events were reported during the study.Conclusions: The sustained-release profile of the test product, compared to reference product, will provide more long-lasting therapeutic effects from a single daily dose (Retrospectively applied on Clinical Trials Registry - India [CTRI]. Application reference number: REF/2020/03/032408). The study reports the unique sustained release formulation of Withania somnifera (Ashwagandha) root extract. The pharmacokinetic study also reports for first time, the successful plasma estimation of withanolide A and 12-deoxywithastraamonolide, the major phytoactives of ashwagandha.

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.

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.

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