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 Intrapulmonary Pharmacokinetics and Pharmacodynamics of Posaconazole at Steady State in Healthy Subjects

2008 ◽  
Vol 53 (2) ◽  
pp. 703-707 ◽  
Author(s):  
John E. Conte ◽  
Jeffrey A. Golden ◽  
Gopal Krishna ◽  
Marina McIver ◽  
Emily Little ◽  
...  
Keyword(s):  
Area Under The Curve ◽  
Healthy Adults ◽  
Pharmacokinetics And Pharmacodynamics ◽  
Open Label ◽  
Multiple Dosing ◽  
Alveolar Cell ◽  
Epithelial Lining Fluid ◽  
Open Label Study ◽  
Dosing Interval ◽  
The Mean

ABSTRACT We evaluated the pharmacokinetics (PK) and pharmacodynamics (PD) of posaconazole (POS) in a prospective, open-label study. Twenty-five healthy adults received 14 doses of POS oral suspension (400 mg twice daily) with a high-fat meal over 8 days. Pulmonary epithelial lining fluid (ELF) and alveolar cell (AC) samples were obtained via bronchoalveolar lavage, and blood samples were collected during the 24 h after the last dose. POS concentrations were determined using liquid chromatography with tandem mass spectrometry parameters. The maximum concentrations (C max) (mean ± standard deviation) in plasma, ELF, and ACs were 2.08 ± 0.93, 1.86 ± 1.30, and 87.7 ± 65.0 μg/ml. The POS concentrations in plasma, ELF, and ACs did not decrease significantly, indicating slow elimination after multiple dosing. The mean concentrations of POS in plasma, ELF, and ACs were above the MIC90 (0.5 μg/ml) for Aspergillus spp. over the 12-h dosing interval and for 24 h following the last dose. Area under the curve from 0 to 12 h (AUC0-12) ratios for ELF/plasma and AC/plasma were 0.84 and 33. AUC0-24/MIC90 ratios in plasma, ELF, and AC were 87.6, 73.2, and 2,860. Nine (36%) of 25 subjects had treatment-related adverse events during the course of the study, which were all mild or moderate. We conclude that a dose of 400 mg twice daily resulted in sustained plasma, ELF, and AC concentrations above the MIC90 for Aspergillus spp. during the dosing interval. The intrapulmonary PK/PD of POS are favorable for treatment or prevention of aspergillosis, and oral POS was well tolerated in healthy adults.

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 Oral Bioavailability and Pharmacokinetics of Trovafloxacin in Patients with AIDS

1999 ◽  
Vol 43 (12) ◽  
pp. 3005-3007 ◽  
Author(s):  
Melinda K. Lacy ◽  
David P. Nicolau ◽  
Charles H. Nightingale ◽  
Amy Geffken ◽  
Renli Teng ◽  
...  
Keyword(s):  
Oral Bioavailability ◽  
Active Form ◽  
Healthy Adults ◽  
Absolute Bioavailability ◽  
Randomized Design ◽  
The Mean

ABSTRACT Trovafloxacin pharmacokinetics were evaluated in 12 subjects with AIDS. By using a randomized design, single 200-mg doses of oral trovafloxacin and intravenous alatrofloxacin were administered. The mean absolute bioavailability was 91%. The pharmacokinetics of trovafloxacin when administered orally as the active form or intravenously as the prodrug (alatrofloxacin) are not altered in subjects with AIDS compared to those in healthy adults.

scholarly journals Pharmacokinetics and Tolerability of Oseltamivir Combined with Probenecid

2008 ◽  
Vol 52 (9) ◽  
pp. 3013-3021 ◽  
Author(s):  
Mark Holodniy ◽  
Scott R. Penzak ◽  
Timothy M. Straight ◽  
Richard T. Davey ◽  
Kelvin K. Lee ◽  
...  
Keyword(s):  
Geometric Mean ◽  
Pharmacokinetic Analysis ◽  
Pharmacokinetic Data ◽  
Oseltamivir Carboxylate ◽  
Versus Group ◽  
Group 3 ◽  
The Mean ◽  
Group 2 ◽  
Mean Concentration ◽  
Group 1

ABSTRACT Oseltamivir is an inhibitor of influenza virus neuraminidase, which is approved for use for the treatment and prophylaxis of influenza A and B virus infections. In the event of an influenza pandemic, oseltamivir supplies may be limited; thus, alternative dosing strategies for oseltamivir prophylaxis should be explored. Healthy volunteers were randomized to a three-arm, open-label study and given 75 mg oral oseltamivir every 24 h (group 1), 75 mg oseltamivir every 48 h (q48h) combined with 500 mg probenecid four times a day (group 2), or 75 mg oseltamivir q48h combined with 500 mg probenecid twice a day (group 3) for 15 days. Pharmacokinetic data, obtained by noncompartmental methods, and safety data are reported. Forty-eight subjects completed the pharmacokinetic analysis. The study drugs were generally well tolerated, except for one case of reversible grade 4 thrombocytopenia in a subject in group 2. The calculated 90% confidence intervals (CIs) for the geometric mean ratios between groups 2 and 3 and group 1 were outside the bioequivalence criteria boundary (0.80 to 1.25) at 0.63 to 0.89 for group 2 versus group 1 and 0.57 to 0.90 for group 3 versus group 1. The steady-state apparent oral clearance of oseltamivir carboxylate was significantly less in groups 2 (7.4 liters/h; 90% CI, 6.08 to 8.71) and 3 (7.19 liters/h; 90% CI, 6.41 to 7.98) than in group 1 (9.75 liters/h; 90% CI, 6.91 to 12.60) (P < 0.05 for both comparisons by analysis of variance). The (arithmetic) mean concentration at 48 h for group 2 was not significantly different from the mean concentration at 24 h for group 1 (42 ± 76 and 81 ± 54 ng/ml, respectively; P = 0.194), but the mean concentration at 48 h for group 3 was significantly less than the mean concentration at 24 h for group 1 (23 ± 26 and 81 ± 54 ng/ml, respectively; P = 0.012). Alternate-day dosing of oseltamivir plus dosing with probenecid four times daily achieved trough oseltamivir carboxylate concentrations adequate for neuraminidase inhibition in vitro, and this combination should be studied further.

scholarly journals Phase I, Open-Label, Single-Dose Study To Evaluate the Pharmacokinetics and Safety of Telbivudine in Children and Adolescents with Chronic Hepatitis B

2013 ◽  
Vol 57 (9) ◽  
pp. 4128-4133 ◽  
Author(s):  
Daniel S. Stein ◽  
June Ke ◽  
Grace Uy ◽  
Miroslava Bosheva ◽  
Yin Qi ◽  
...  
Keyword(s):  
Chronic Hepatitis ◽  
Single Dose ◽  
Hepatitis B ◽  
Phase I ◽  
Children And Adolescents ◽  
Chronic Hepatitis B ◽  
Healthy Adults ◽  
Pharmacokinetic Data ◽  
Open Label ◽  
Time Profiles

ABSTRACTTelbivudine is a nucleoside analogue that has been approved for the treatment of chronic hepatitis B virus (HBV) infection in adults at 600 mg/day. We conducted a phase I, open-label, first-in-pediatrics study to investigate the safety and pharmacokinetics of a single dose of telbivudine in HBV-infected children and adolescents. Eligible patients were enrolled sequentially from older to younger groups, with evaluation of safety and available pharmacokinetic data after each stratum. Adolescent patients (>12 to 18 years) received a single dose of 600 mg telbivudine as an oral solution, while children aged 2 to 12 years received a single dose of 15 or 25 mg/kg of body weight up to a maximum of 600 mg. Telbivudine was well tolerated; all adverse events were mild, and none occurred in more than one patient. The plasma telbivudine concentration-versus-time profiles in adolescents given 600 mg were similar to the mean profile of healthy adults receiving the same oral dose. Children aged 2 to <6 and 6 to 12 years receiving a single 15-mg/kg dose showed similar plasma exposures. To predict the steady-state exposure, plasma concentration-versus-time profiles for patients aged 2 to 12 years (15 mg/kg) and >12 to 18 years (600 mg) were fitted to a two-compartment 1st-order, microconstant, lag time, 1st-order elimination pharmacokinetic (PK) model. This analysis predicted the following dosages to mimic exposures in healthy adults receiving 600 mg/day: 20 mg/kg/day for children 2 to 12 years and 600 mg/day for adolescents. Studies are ongoing to evaluate the efficacy of the recommended dose in pediatric patients. (This study has been registered at ClinicalTrials.gov under registration no. NCT00907894.)

scholarly journals Pharmacokinetics of a Novel Form of Biotin, Magnesium Biotinate, in Healthy Subjects (P06-027-19)

2019 ◽  
Vol 3 (Supplement_1) ◽  
Author(s):  
Sara Perez Ojalvo ◽  
Sarah Sylla ◽  
James Komorowski
Keyword(s):  
Clinical Study ◽  
Peak Plasma ◽  
Plasma Concentrations ◽  
Area Under The Curve ◽  
Blood Levels ◽  
Pharmacokinetic Data ◽  
Open Label ◽  
Post Dose ◽  
Funding Sources ◽  
Study Results

Abstract Objectives Biotin, also known as vitamin B7, plays an important role in the metabolization of nutrients into energy. Magnesium biotinate (MgB) is a novel biotin compound that has been shown to be 40 times more soluble than D-Biotin. Preclinical evidence has shown that MgB is well absorbed into the bloodstream and tissues, particularly the brain, over time. The following pharmacokinetic study was carried out to further explore the absorption and bioavailability of MgB. Methods In an open-label clinical study, 30 healthy female subjects (18–45 years, BMI 18.0–29.9 kg/m2) were randomized to receive a single oral capsule containing one of the following doses of MgB (n = 10 per group): 1) 10 mg MgB, 2) 40 mg MgB, 3) 100 mg MgB. Serial blood samples were collected in K2-EDTA tubes at pre-dose (within 1 hour of dose) and at 0.5, 1.0, 1.5, 3.0 and 6.0 hours post-dose. Plasma samples were analyzed for biotin by LC/MS/MS. Pharmacokinetic data were calculated for each dose group. Results Study results showed that plasma biotin levels increased at 0.5, 1.0, 1.5, 3.0 and 6.0 hours post-dose for all groups. However, the largest biotin increase was seen in the 100 mg group (Figure 1). Peak plasma concentrations were observed as follows: 84.8 ng/mL 1 hour after a 10 mg dose, 214.6 ng/mL 1.5 hours after a 40 mg dose, and 508.5 ng/mL 1.5 hours after a 100 mg dose. Area under the curve values increased with increasing biotin dose level (10 mg: 210.0 ng*h/mL; 40 mg: 605.1 ng*h/mL; 100 mg: 1652.4 ng*h/mL). No adverse effects were observed. Conclusions Results from this single-dose pharmacokinetic clinical study demonstrate that magnesium biotinate is a bioavailable form of biotin, with increasing blood levels associated with increasing dose levels. Funding Sources This study was funded by JDS Therapeutics, LLC. Supporting Tables, Images and/or Graphs

scholarly journals Novel Population Pharmacokinetic Method Compared to the Standard Noncompartmental Approach to Assess Bioequivalence of Iron Gluconate Formulations

2013 ◽  
Vol 16 (3) ◽  
pp. 424 ◽  
Author(s):  
Corinne Seng Yue ◽  
Keith Gallicano ◽  
Line Labbé ◽  
Murray P Ducharme
Keyword(s):  
Compartmental Model ◽  
Area Under The Curve ◽  
Relative Bioavailability ◽  
Population Pharmacokinetic ◽  
Noncompartmental Analysis ◽  
Open Label ◽  
Post Dose ◽  
Final Model ◽  
Pharmacokinetic Properties ◽  
Noncompartmental Approach

Purpose: Iron-containing products are atypical in terms of their pharmacokinetic properties because iron is only removed by plasma sampling and is non-linear. This study aims to present a novel way of assessing the relative bioavailability of two sodium ferric gluconate complex (SFGC) formulations and compare this approach to a standard previously published noncompartmental approach. Methods: Data were from open-label, randomized, single-dose studies (Study 1 was parallel whereas Study 2 was crossover). Subjects with low but normal iron levels were infused IV SFGC in sucrose by GeneraMedix Inc. and/or Ferrlecit ® Injection (Watson Laboratories Inc.). In Study 1 (n=240), 125 mg was infused over 10 minutes. In Study 2 (n=29), 62.5 mg was infused over 30 minutes. Samples were assayed for total iron (TI) and transferrin-bound iron (TBI) over 36 hours (Study 1) or 72 hours (Study 2) post-dose. Studies 1 and 2 used standard noncompartmental analysis. Study 2 also used population PK (PPK) analyses with ADAPT 5®. The final model predicted SFGC area-under-the-curve (AUCpred) and maximal concentration (Cmaxpred). Analyses of variance was conducted on ln-transformed PK parameters. Ratios of means and 90% confidence intervals (CIs) were estimated. Bioequivalence was demonstrated if values were within 80-125%. Results: For Study 1, ratios and 90% CIs for TI baseline-corrected Cmax and AUC0-36 were 100.4 (96.5 – 104.5) and 99.7 (94.2 – 105.5). For TBI, results for TI baseline-corrected Cmax and AUC0-36 were 86.8 (82.7 – 91.1) and 92.4 (85.6 – 99.7). For Study 2, a multi-compartmental model simultaneously described the PK of TI, TBI and SFGC. Ratios and 90% CIs for SFGC Cmaxpred and AUCpred were 89.9 (85.9 - 94.0) and 89.7 (85.7 - 93.9), while ratios and 90% CI obtained from the noncompartmental analysis of Study 2 did not meet BE criteria because of low power. Conclusions: Both the standard and PPK modeling approach suggested bioequivalence between the iron products. However, with the PPK method, less subjects were required to meet study objectives compared to the standard noncompartmental approach which required considerably more subjects (29 vs 240). 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.

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