Single-dose Pharmacokinetic Properties and Relative Bioavailability of a Novel Methylphenidate Extended-release Chewable Tablet Compared With Immediate-release Methylphenidate Chewable Tablet

2016 ◽  
Vol 38 (5) ◽  
pp. 1151-1157 ◽  
Author(s):  
Richat Abbas ◽  
Donna Palumbo ◽  
Faith Walters ◽  
Heidi Belden ◽  
Sally A. Berry
Keyword(s):  
Single Dose ◽  
Extended Release ◽  
Immediate Release ◽  
Relative Bioavailability ◽  
Chewable Tablet ◽  
Pharmacokinetic Properties

scholarly journals Benznidazole Extended-Release Tablets for Improved Treatment of Chagas Disease: Preclinical Pharmacokinetic Study

2016 ◽  
Vol 60 (4) ◽  
pp. 2492-2498 ◽  
Author(s):  
Marcelo Gomes Davanço ◽  
Michel Leandro Campos ◽  
Talita Atanazio Rosa ◽  
Elias Carvalho Padilha ◽  
Alejandro Henao Alzate ◽  
...  
Keyword(s):  
Chagas Disease ◽  
Extended Release ◽  
Hydroxypropyl Methylcellulose ◽  
Immediate Release ◽  
Relative Bioavailability ◽  
Pharmacokinetic Parameters ◽  
Therapeutic Success ◽  
Preclinical Pharmacokinetics ◽  
Bioavailability Study

ABSTRACTBenznidazole (BNZ) is the first-line drug for the treatment of Chagas disease. The drug is available in the form of immediate-release tablets for 100-mg (adult) and 12.5-mg (pediatric) doses. The drug is administered two or three times daily for 60 days. The high frequency of daily administrations and the long period of treatment are factors that significantly contribute to the abandonment of therapy, affecting therapeutic success. Accordingly, this study aimed to evaluate the preclinical pharmacokinetics of BNZ administered as extended-release tablets (200-mg dose) formulated with different types of polymers (hydroxypropyl methylcellulose K4M and K100M), compared to the tablets currently available. The studies were conducted with rabbits, and BNZ quantification was performed in plasma and urine by ultraperformance liquid chromatography methods previously validated. The bioavailability of BNZ was adequate in the administration of extended-release tablets; however, with the administration of the pediatric tablet, the bioavailability was lower than with other tablets, which showed that the clinical use of this formulation should be monitored. The pharmacokinetic parameters demonstrated that the extended-release tablets prolonged drug release from the pharmaceutical matrix and provided an increase in the maintenance of the drug concentrationin vivo, which would allow the frequency of administration to be reduced. Thus, a relative bioavailability study in humans will be planned for implementation of a new product for the treatment of Chagas disease.

scholarly journals Single-dose pharmacokinetics of amphetamine extended-release tablets compared with amphetamine extended-release oral suspension

CNS Spectrums ◽  
2020 ◽  
Vol 25 (6) ◽  
pp. 774-781
Author(s):  
Antonio Pardo ◽  
Judith C. Kando ◽  
Thomas R. King ◽  
Eman Rafla ◽  
Barry K. Herman
Keyword(s):  
Single Dose ◽  
Adverse Events ◽  
Extended Release ◽  
Food Effect ◽  
Relative Bioavailability ◽  
Oral Suspension ◽  
Plasma Samples ◽  
Serious Adverse Events ◽  
Time Points ◽  
Extended Release Tablet

AbstractObjectiveEvaluate the relative bioavailability of single-dose amphetamine extended-release tablet (AMPH ER TAB) 20 mg, swallowed whole or chewed, and amphetamine extended-release oral suspension (AMPH EROS) 2.5 mg/mL; evaluate food effect on AMPH ER TAB.MethodsHealthy volunteers (18–55 years) were randomized to 1 dose of AMPH ER TAB 20 mg swallowed (fasted), chewed (fed/fasted), or 20 mg AMPH EROS (fasted). A crossover study design was used. Plasma samples were collected each period predose and at time points to 60 hours postdose. d- and l-amphetamine were measured and pharmacokinetic (PK) was calculated (90% confidence intervals of the ratios of the plasma levels) for AUC0-t, AUC0-∞, and Cmax. Comparative relative bioavailability between formulations was determined when ratios were within 80% and 125%. Safety was also assessed.ResultsThirty-two subjects completed the study. AMPH ER TAB swallowed versus AMPH EROS (fasted): for d- and l-amphetamine, the total and peak exposure was similar: d: AUC0-t: 100.68% to 108.08%, AUC0-∞: 101.47% to 109.52%, Cmax: 98.10% to 103.17%; l: AUC0-t: 100.31% to 108.57%, AUC0-∞: 101.27% to 111.09%, Cmax: 98.2% to 103.37%. For d- and l-amphetamine when the tablet is swallowed whole, Tmax was 5.00 hours (with a range of 2.00–9.00 hours). AMPH ER TAB chewed versus AMPH EROS (fasted): for d- and l-amphetamine, the total and peak exposure was similar: d: AUC0-t: 99.23% to 106.62%, AUC0-∞: 99.58% to 107.59%, Cmax: 99.91% to 105.14%; l: AUC0-t: 98.16% to 106.35%, AUC0-∞: 98.44% to 108.11%, Cmax: 99.53% to 104.75%. For d- and l-amphetamine when the tablet has been chewed, Tmax was 5.00 hours (with a range of 3.00-7.00 hours). PK results were similar for patients in the fasted and fed groups, indicative of no presence of food effect. No serious adverse events (AEs) were reported, overall AE profiles between the tablet and oral suspension were comparable without any unanticipated safety concerns.ConclusionsSingle doses of AMPH ER TAB for both d- and l-amphetamine demonstrated comparable bioavailability to a 20 mg dose of AMPH EROS, 2.5 mg/mL under fasted conditions when chewed and swallowed whole, and demonstrated equivalent peak and overall exposure without apparent food effect. AMPH ER TAB was well-tolerated and consistent with adverse events noted in other amphetamine formulations.

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.

A pharmacokinetic evaluation of single and multiple doses of extended-release hydrocodone bitartrate in subjects experiencing surgical or osteoarthritic pain

2015 ◽  
Vol 11 (5) ◽  
pp. 405 ◽  
Author(s):  
Cynthia Y. Robinson, PhD ◽  
Christopher M. Rubino, PharmD ◽  
Stephen J. Farr, PhD
Keyword(s):  
Single Dose ◽  
Steady State ◽  
Extended Release ◽  
Venous Blood ◽  
Plasma Concentrations ◽  
Immediate Release ◽  
Pharmacokinetic Parameters ◽  
Single Dose Study ◽  
Dosing Interval ◽  
Osteoarthritic Pain

Objectives: To assess the single-dose and steady-state pharmacokinetics of a single-entity hydrocodone extended-release (ER) formulation in patients enrolled in two separate phase 2 clinical studies.Setting: Both studies were multicenter clinical studies.Subjects and interventions: In study 1, 115 subjects with postsurgical pain (bunionectomy) received single doses of 10, 20, 30, or 40 mg hydrocodone-ER, 10 mg hydrocodone/325 mg acetaminophen immediate-release (IR), or placebo. In study 2, 37 subjects with osteoarthritic pain received doses of 10, 20, 30, or 40 mg of hydrocodone-ER twice-daily for 7 days. Venous blood samples were taken periodically up to 24 hours postdosing after the single dose (study 1) or after 7 days of dosing (study 2) and were assayed for concentrations of hydrocodone and its major metabolites.Main outcome measures: Standard pharmacokinetic parameters were estimated by noncompartmental analysis methods.Results: Following a single dose of hydrocodone-ER, Tmax was prolonged to approximately 6 hours at all dose levels of hydrocodone-ER compared with 2.9 hours for the IR formulation. All doses of hydrocodone-ER formulations provided prolonged and sustained release of hydrocodone throughout the 12-hour dosing interval with reduced peak-to-trough fluctuation at steady state compared with hydrocodone/acetaminophen-IR comparator. Both single-dose and steady-state mean Cmax and AUClast values showed reasonable dose-proportionality. Norhydrocodone and hydromorphone plasma concentrations were 32-38 percent and <2.1 percent, respectively, of hydrocodone concentrations in both studies.Conclusions: The sustained plasma concentrations of hydrocodone support twice-daily dosing with a 12-hour dosing interval.

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