scholarly journals Comparison of Azithromycin Pharmacokinetics following Single Oral Doses of Extended-Release and Immediate-Release Formulations in Children with Acute Otitis Media

2011 ◽  
Vol 55 (11) ◽  
pp. 5022-5026 ◽  
Author(s):  
Ping Liu ◽  
Annie F. Fang ◽  
Robert R. LaBadie ◽  
Penelope H. Crownover ◽  
Adriano G. Arguedas
Keyword(s):  
Single Dose ◽  
Otitis Media ◽  
Extended Release ◽  
Geometric Mean ◽  
Acute Otitis Media ◽  
Lower Boundary ◽  
Systemic Exposure ◽  
Immediate Release ◽  
Oral Suspension ◽  
Tolerability Profile

ABSTRACTAn azithromycin extended-release (ER) oral suspension was developed to improve the gastrointestinal tolerability profile without substantially compromising systemic exposure. A single dose of 30 mg/kg azithromycin immediate-release (IR) oral suspension has been used in children to treat acute otitis media (AOM). This study was conducted to compare the pharmacokinetics of a 60-mg/kg azithromycin ER single dose with a 30-mg/kg azithromycin IR single dose in children with AOM aged 6 months to 6 years (n= 19 per treatment). Serum samples were collected at 1, 2, 3, 4, 8, 24, 48, and 72 h after dosing. The area under the curve from time zero to 72 h postdosing (AUC0-72) was calculated based on a noncompartmental method. One-way analysis of variance (ANOVA) was used to compare exposure parameters (e.g., AUC0-72and peak concentration) as well as concentrations at each time point. The adjusted geometric mean ratio of the ER/IR AUC0-72was 157.98% (90% confidence interval [CI], 98.87%, 252.44%), which met the predefined criterion of the lower boundary of the 90% CI of ≥80%. As expected, due to the slower-release profile of the ER formulation, the concentrations of the ER formulation during the first 3 h were lower than those of the IR formulation. After 3 h postdosing, the lower boundaries of the 90% CI for the ER/IR concentration ratios were greater than 100%. These results indicated that a 60-mg/kg single dose of ER azithromycin provides similar or greater systemic exposure in children than the 30-mg/kg single dose of IR azithromycin.

scholarly journals 178 Single-Dose Pharmacokinetics of Amphetamine Extended-Release Tablet Compared with Amphetamine Extended-Release Oral Suspension

CNS Spectrums ◽  
2020 ◽  
Vol 25 (2) ◽  
pp. 312-313
Author(s):  
Barry K. Herman ◽  
Judith C. Kando ◽  
Thomas King ◽  
Antonio Pardo
Keyword(s):  
Single Dose ◽  
Extended Release ◽  
Food Effect ◽  
Geometric Mean ◽  
Oral Suspension ◽  
Post Dose ◽  
Comparative Bioavailability ◽  
Extended Release Tablet ◽  
Funding Acknowledgements ◽  
Release Tablet

Abstract:Objectives:Evaluate comparative bioavailability of single-dose amphetamine extended-release tablet (AMPH ER TAB, Tris Pharma, Inc., Monmouth Junction, NJ) 20 mg, swallowed whole or chewed and amphetamine extended-release oral suspension (AMPH EROS) 2.5 mg/mL; and evaluate whether a PK food effect exists on AMPH ER TAB (contains a 3.2:1 ratio of d- to l-amphetamine).METHODS:Healthy volunteers (18-55 yr) were randomized to 1 dose of AMPH ER TAB 20 mg swallowed (fasted), chewed (fed/fasted), or 20 mg AMPH EROS (fasted).A crossover design was used. Samples were collected each period pre-dose and at time points to 60 h post-dose. D-and l-amphetamine were measured, and PK was calculated (90% CIs of the ratios of the geometric mean plasma levels) for Cmax, AUCt, and AUC0∞. Comparative bioavailability was determined when ratios were within 80 and 125%. Safety was also assessed.RESULTS:32 subjects completed the study. Based on the calculated bioavailability ratios, for AMPH ER TAB swallowed vs. AMPH EROS fasted: d-amphetamine total and peak exposures were found to be similar: AUC0-t: 100.68-108.08%, AUC0-∞:101.47-109.52%, Cmax: 98.10-103.17%. For l-amphetamine, the total and peak exposures were similar: AUC0-t: 100.31-108.57%, AUC0-∞:101.27-111.09%, Cmax: 98.2-103.37%.AMPH ER TAB chewed vs. AMPH EROS fasted: For d-amphetamine, the total and peak exposures were similar: AUC0-t: 99.23-106.62%, AUC0-∞: 99.58-107.59%, Cmax: 99.91-105.14%. For l-amphetamine, the total and peak exposure was similar: AUC0-t: 98.16-106.35%, AUC0-∞: 98.44-108.11%, Cmax: 99.53-104.75%.Food effect: AMPH ER TAB, chewed, fasted vs. fed: For d-amphetamine, the total and peak exposure was similar: AUC0-t: 92.57-99.49%, AUC0-∞: 91.12-98.48%, Cmax: 94.22-99.17%.For l-amphetamine, the total and peak exposure was similar: AUC0-t: 91.27-98.91%, AUC0-∞: 88.44-97.17%, Cmax: 94.52-99.50%).No serious AEs were reported during the conduct of this study, and the AE profiles were observed to be similar in frequency of events and severity to other amphetamine formulations used in ADHD.CONCLUSIONS:Bioavailability of single dose of AMPH ER TAB for both d- and l-amphetamine was comparable, swallowed whole or chewed, to an equivalent 20 mg dose of the reference product AMPH EROS, 2.5 mg/mL fasted, and showed equivalent peak and overall exposure.No food effect was observed for AMPH ER TAB administered chewed. All AEs were mild in severity and AE profiles were similar to other amphetamine formulations used for treatment of ADHD.Funding Acknowledgements:Tris Pharma, Inc.

Single-Dose Intramuscular Ceftriaxone for Acute Otitis Media in Children

PEDIATRICS ◽  
1993 ◽  
Vol 91 (1) ◽  
pp. 23-30
Author(s):  
Steven M. Green ◽  
Steven G. Rothrock
Keyword(s):  
Single Dose ◽  
Confidence Interval ◽  
Otitis Media ◽  
Intramuscular Injection ◽  
Acute Otitis Media ◽  
Oral Suspension ◽  
Double Blind ◽  
Double Blind Clinical Trial ◽  
Single Intramuscular Injection

This study evaluated the efficacy of a single dose of intramuscular ceftriaxone for acute otitis media in children, using amoxicillin as a control. (There is currently no established single-dose treatment for this condition.) In a prospective, randomized, double-blind, clinical trial, 233 children, aged 5 months to 5 years, with uncomplicated acute otitis media were randomly assigned to receive either a single intramuscular injection of ceftriaxone (50 mg/kg) plus placebo oral suspension for 10 days, or a placebo injection plus amoxicillin oral suspension (40 mg/kg per day divided three times per day) for 10 days in a double-blind fashion. Demographic and clinical characteristics were similar in both groups. Treatment was successful in 107 of 117 given amoxicillin (91%, 95% confidence interval 86% to 97%) and 105 of 116 given ceftriaxone (91%, 95% confidence interval 85% to 96%). Rates of improvement, failure, relapse, and reinfection were similar in both groups, as were the otoscopic and tympanometric evaluations at the 14- and 60-day follow-up visits. It is concluded that a single intramuscular injection of ceftriaxone (50 mg/kg) is as effective as 10 days of oral amoxicillin for the treatment of uncomplicated acute otitis media in children.

scholarly journals Comparative Bioavailability of Amphetamine Extended-Release Oral Suspension and Extended-Release Mixed Amphetamine Salts

CNS Spectrums ◽  
2021 ◽  
Vol 26 (2) ◽  
pp. 163-163
Author(s):  
Antonio Pardo ◽  
Mohammed Bouhajib ◽  
Eman Rafla ◽  
Thomas R. King ◽  
Judith C. Kando
Keyword(s):  
Single Dose ◽  
Safety Assessment ◽  
Extended Release ◽  
Healthy Adult ◽  
Geometric Mean ◽  
Oral Suspension ◽  
Open Label ◽  
Post Dose ◽  
Comparative Bioavailability ◽  
The Mean

AbstractPurposeThis open-label, single-dose, randomized, two-period, two-treatment, two-sequence, crossover study evaluated the comparative bioavailability between amphetamine extended-release oral suspension (treatment A: AMPH EROS, Dyanavel XR 2.5 mg/mL, 18.8 mg amphetamine base per 7.5 mL) and extended-release mixed amphetamine salts (treatment B: ER MAS, Adderall XR 30 mg capsules, equivalent to 18.8 mg amphetamine base per capsule) after a single dose in healthy adult subjects, under fasted conditions.MethodsThe crossover design allowed for intra-subject PK comparisons. Relative comparable bioavailability was determined by a statistical comparison of the AUC and Cmax parameters for both d- and l-amphetamine, where the geometric mean ratios for AUC and Cmax were within the 90% confidence limits (80.0%–125.0%) to determine comparable bioavailability between test products. Subjects in sequence 1 received treatment A followed by B; subjects in sequence 2 received treatment B followed by treatment A. PK samples were obtained at 0 (pre-dose) through 60 hours post-dose. The safety assessment was based on reported frequency and severity of adverse events.ResultsThirty (30) subjects were enrolled and 28 completed. The mean age of subjects was 35 years, with a mean BMI of 25.9 kg/m2. Most subjects were Male (63.3%) and Black (56.7%). The geometric mean ratios for Cmax and all AUC measurements were within the 80–125% bound indicating comparable bioavailability between both test products. Both test products were generally well-tolerated with no serious AEs reported.ConclusionsThe bioavailability of a single 7.5 mL dose of AMPH EROS 2.5 mg/mL was comparable to a single 30 mg capsule dose of ER MAS. AMPH EROS (both d- and l-amphetamine) showed equivalent peak and overall exposure to ER MAS under fasted conditions.FundingTris Pharma, Inc.

Comparison of Cefpodoxime Proxetil and Cefixime in the Treatment of Acute Otitis Media in Infants and Children

PEDIATRICS ◽  
1994 ◽  
Vol 94 (6) ◽  
pp. 847-852
Author(s):  
Basim I. Asmar ◽  
Adnan S. Dajani ◽  
Mark A. Del Beccaro ◽  
Paul M. Mendelman ◽  
Keyword(s):  
Otitis Media ◽  
Acute Otitis Media ◽  
Drug Efficacy ◽  
Oral Suspension ◽  
Suppurative Otitis Media ◽  
Once Daily ◽  
Cefpodoxime Proxetil ◽  
Long Term Follow Up ◽  
Cure Rates

Objective. To compare the use of once-a-day cefpodoxime proxetil to once-a-day cefixime in the treatment of acute suppurative otitis media. Design. Randomized, multicenter, investigator-blinded. Setting. Outpatient. Patients. A total of 368 patients (age 2 months to 17 years) were randomized to receive either cefpodoxime or cefixime in a 2:1 ratio (245 cefpodoxime, 123 cefixime); 236 patients (155 cefpodoxime, 81 cefixime) were evaluable for drug efficacy. Interventions. Patients received either cefpodoxime proxetil oral suspension (10 mg/kg/day, once daily for 10 days) or cefixime oral suspension (8 mg/kg/day, once daily for 10 days). Main outcome measures. Clinical evaluations were performed before treatment (study day 1), at an interim visit (study day 3 through 6), at the end of therapy (study day 12 through 15), and at final follow-up (study day 25 through 38). Microbiologic evaluations were performed at enrollment and whenever appropriate thereafter. Results. End-of-therapy clinical cure rates in evaluable patients were 56% for the cefpodoxime group and 54% for the cefixime group. Clinical improvement rates were 27% for both groups. Clinical response rates were not significantly different between treatment groups (P = .541; 95% confidence interval = -8.1%, 15.2%). At long-term follow-up, 17% of patients in the cefpodoxime group and 20% in the cefixime group had a recurrence of infection. Drug-related adverse events (eg, diarrhea, diaper rash, vomiting, rash) occurred in 23.3% of cefpodoxime-treated patients and 17.9% of cefixime-treated patients (P = .282). Conclusions. These findings suggest that cefpo-doxime proxetil administered once daily is as effective and safe as cefixime given once daily in the treatment of acute suppurative otitis media in pediatric patients.

scholarly journals A randomized, phase IIa study to assess the systemic exposure of triamcinolone acetonide following injection of extended-release triamcinolone acetonide or traditional triamcinolone acetonide into both knees of patients with bilateral knee osteoarthritis

2019 ◽  
Vol 11 ◽  
pp. 1759720X1988130 ◽  
Author(s):  
Alan Kivitz ◽  
Louis Kwong ◽  
Tammi Shlotzhauer ◽  
Joelle Lufkin ◽  
Amy Cinar ◽  
...  
Keyword(s):  
Knee Osteoarthritis ◽  
Triamcinolone Acetonide ◽  
Extended Release ◽  
Peak Plasma ◽  
Geometric Mean ◽  
Systemic Exposure ◽  
Pharmacokinetic Analysis ◽  
Bilateral Knee ◽  
American College Of Rheumatology ◽  
Crystalline Suspension

Background: Intra-articular corticosteroids are commonly used for pain relief in patients with knee osteoarthritis. Simultaneous intra-articular corticosteroid (CS) knee injections may be beneficial for the ~80–90% of patients who present with, or develop, bilateral knee osteoarthritis, but concurrent injections may increase systemic CS exposure and data on safety/tolerability are lacking. Triamcinolone acetonide extended release (TA-ER) has shown decreased systemic triamcinolone acetonide exposure compared with traditional triamcinolone acetonide crystalline suspension (TAcs) after a single knee injection in patients with knee osteoarthritis. This phase IIa study was designed to assess the safety and systemic triamcinolone acetonide exposure following injections of TA-ER or TAcs into each knee of patients with bilateral knee osteoarthritis. Methods: Patients (⩾40 years) meeting American College of Rheumatology criteria for knee osteoarthritis in both knees received concurrent single intra-articular injections of TA-ER 32 mg or TAcs 40 mg into each knee (total: 64 mg and 80 mg, respectively) and were followed for 6 weeks. Safety was evaluated based on treatment-emergent adverse events (TEAEs). Blood samples for pharmacokinetic analysis were collected pre-injection, and at the following postinjection time points: 1, 2, 3, 4, 5, 6, 8, 10, 12, and 24 h, and days 8, 15, 29, and 43. Results: Baseline characteristics were balanced between patients randomly assigned to TA-ER ( n = 12) or TAcs ( n = 12). Both treatments were well tolerated with comparable TEAE profiles. Peak plasma triamcinolone acetonide concentrations (Cmax) were lower following bilateral TA-ER injections [geometric mean, 2277.7 pg/ml (95% CI, 1602.13–3238.04)] compared with bilateral TAcs injections [7394.7 pg/ml (2201.06–24,843.43)], with median times to Cmax (Tmax) of 4.5 and 6.5 h, respectively. Conclusions: In patients with bilateral knee osteoarthritis, intra-articular injection of TA-ER into both knees was well tolerated. Consistent with pharmacokinetic profiles observed after a single knee injection, plasma triamcinolone acetonide concentrations were lower after bilateral TA-ER injections compared with the higher and more variable concentrations observed after bilateral TAcs injections. ClinicalTrials.gov identifier: NCT03378076

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