Bioequivalence assessment of Azomycin® (Julphar, UAE) as compared to Zithromax® (Pfizer, USA)—two brands of azithromycin—in healthy human volunteers

Najib, Naji M.; Idkaidek, Nasir; Ghanem, Iz-Eddein; Admour, Isra'; Alam, S. Mahmood; Zaman, Qamar; Dham, Ruwayda

doi:10.1002/bdd.252

Cited by 12 publications

(8 citation statements)

References 21 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Furthermore, intrasubject variabilities in C max were found to be 39.7% and 42.6% for the test and reference formulations, respec- tively, while intrasubject variabilities in AUC 0-72 were recorded as 37.7% and 34.5% for the test and reference formulations, respectively. T max achieved comparable results with those reported in previous bioequivalence studies of a single-dose azithromycin tablet 26,27 and capsule 28,29 in Asian and Southeast Asian populations.…”

Section: Resultssupporting

confidence: 78%

Pharmacokinetics and Bioequivalence of 2 Azithromycin Tablet Formulations: A Randomized, Open‐Label, 2‐Stage Crossover Study in Healthy Volunteers

Leong¹,

Yee²,

Nalaiya³

et al. 2022

Clinical Pharm in Drug Dev

View full text Add to dashboard Cite

The current study aimed to assess the bioequivalence of a new branded azithromycin with the reference formulation. An open-label, randomized, 2-stage, crossover study design was implemented involving 77 healthy volunteers under fasting conditions. Each volunteer received a single dose of 250-mg azithromycin tablets test and reference formulations separated by a 21-day washout period. Twenty-two samples were collected at pre-dose and until 72 hours post-dose. Azithromycin concentrations were analyzed using a high-performance liquid chromatography-mass spectrometry validated method following a solid-phase plasma extraction. Noncompartmental analysis was carried out to estimate the pharmacokinetic parameters, which were compared between the test and reference products using a multivariate analysis of variance. The difference between C max and AUC 0-72 of the test and reference formulation was not significant. The 94.1% confidence intervals of ln-transformed C max and AUC 0-72 of azithromycin were within the bioequivalence acceptance limits of 80%-125%, therefore it can be concluded that the tested formulation is bioequivalent to the reference formulation.

show abstract

Section: Resultssupporting

confidence: 78%

Pharmacokinetics and Bioequivalence of 2 Azithromycin Tablet Formulations: A Randomized, Open‐Label, 2‐Stage Crossover Study in Healthy Volunteers

Leong¹,

Yee²,

Nalaiya³

et al. 2022

Clinical Pharm in Drug Dev

View full text Add to dashboard Cite

show abstract

“…[9][10][11] These approaches are similar in principle but differ in detail. Compared with other reported BE of azithromycin, [12][13][14][15] a significant difference of this study is that the BE was evaluated using the referencescaled BE (RSABE) approach with a partial replicate design. The RSABE approach adjusts the BE limits of highly variable drugs by scaling to the within-subject variability of the reference product in the study and imposes a limit of 0.8 to 1.25 on the geometric mean ratio.…”

Section: Discussionmentioning

confidence: 99%

A Reference‐Scaled Average Bioequivalence Study of Azithromycin Tablets Manufactured in China and the United States: An Open‐Label, Randomized, Single‐Dose, 3‐Way Crossover Study in Healthy Chinese Subjects Under Fasted and Fed Conditions

Wei

et al. 2022

Clinical Pharm in Drug Dev

View full text Add to dashboard Cite

Azithromycin (Zithromax) is an azalide antibiotic that binds to the 50S ribosomal subunit of the susceptible organism and thereby interferes with its protein synthesis. An open-label, randomized, single-dose, 3-way crossover bioequivalence study was conducted to compare the rate and extent of absorption of the azithromycin 250-mg tablet manufactured at Pfizer Dalian (China) and that at Pfizer Barceloneta (United States) under fasted and fed conditions in healthy Chinese subjects.This study aimed to support a generic consistency evaluation program,initiated by the National Medical Products Administration, for evaluating the quality and efficacy of the products manufactured in China. In the study, the withinsubject standard deviation for area under the serum concentration-time profile from time 0 to 72 hours after dosing in the fasted condition was <0.294, and the 90%CI for the ratio was within 80% to 125%; the within-subject SDs for serum peak concentration in the fasted condition, area under the serum concentration-time profile from time 0 to 72 hours after dosing in the fed condition, and serum peak concentration in the fed condition, were all >0.294, with the upper confidence bounds being <0.00, and the point estimates of the ratios being within 80% to 125%. The results support the bioequivalence between azithromycin tablets manufactured in China and the United States in fasted and fed conditions, with both tablets showing an acceptable safety/tolerability profile in the studied population.

show abstract

“…Unlike clindamycin, the antibiotic azithromycin (AZ) possesses wider therapeutic applications (8) and has pharmacokinetic properties that are characterized by more extensive tissue distribution, prolonged phagocyte concentrations, and a longer elimination half-life of about 50 h (1,14). These favorable features allow once-daily dosing with AZ compared with multiple daily dosing with clindamycin.…”

mentioning

confidence: 99%

Pharmacokinetics and Ex Vivo Antimalarial Activity of Artesunate-Azithromycin in Healthy Volunteers

Chinh

Quang

Anh

et al. 2011

Antimicrob Agents Chemother

View full text Add to dashboard Cite

In 18 male healthy subjects, artesunate (200 mg)-azithromycin (1,500 mg) daily for 3 days was found to be well tolerated, with only mild gastrointestinal disturbances reported. The pharmacokinetic properties of artesunate-azithromycin given in combination are comparable to those of the drugs given alone. Artesunate and its major active metabolite, dihydroartemisinin, are responsible for most of the ex vivo antimalarial activity, with a delayed contribution by azithromycin.Artemisinin-based combination therapies (ACTs) are currently recommended for the first-line treatment of uncomplicated Plasmodium falciparum malaria, worldwide (25). The two risk groups most vulnerable to malaria are young children and pregnant women, who are immunosuppressed and particularly at risk for severe disease (26). In pregnant women, limited safety and pharmacological data are available on the use of ACTs, particularly during the first trimester. The World Health Organization (WHO) recommends that quinine combined with the antibiotic clindamycin be given for 7 days during the first trimester and, if quinine-clindamycin is either unavailable or fails, an ACT is indicated (25). Historically, 7-day daily regimens are limited by poor compliance in an outpatient setting (9). For the second and third trimesters, WHO recommends artesunate (AS)-clindamycin.However, a drawback in using clindamycin is its short halflife of 2.4 h (10), which necessitates repeated dosing every 12 h, which may affect compliance and thus effectiveness (20). Unlike clindamycin, the antibiotic azithromycin (AZ) possesses wider therapeutic applications (8) and has pharmacokinetic properties that are characterized by more extensive tissue distribution, prolonged phagocyte concentrations, and a longer elimination half-life of about 50 h (1, 14). These favorable features allow once-daily dosing with AZ compared with multiple daily dosing with clindamycin. Recently, 3-day courses of quinine with either 1,000 or 1,500 mg AZ were shown to be well tolerated and effective in curing multidrug-resistant P. falciparum malaria in adults (12). AZ also has a good safety profile in children and pregnant women (6, 21).Because of AZ's favorable pharmacokinetic properties, artesunate (AS) plus AZ may be a suitable ACT during pregnancy. In vitro studies have shown dihydroartemisinin (DHA), the active metabolite of the prodrug AS, combined with AZ to be additive (17) tending to synergistic (16) against multidrugresistant P. falciparum strains. Recent studies of AS-AZ have shown good efficacy in the treatment of uncomplicated falciparum malaria using 3-day regimens of 200 mg AS daily with either 1,000 mg AZ (cure rate, 89%) (15) or 1,500 mg AZ (cure rates, Ͼ92%) (15, 24). The AS-AZ combinations are far more effective than monotherapy, with recrudescence rates of between 10% and 80% with 3-to 5-day courses of AS alone (4) and 67% with 1,000 mg/day AZ for 3 days (7). Similarly, the addition of AZ (1,000 mg daily for 2 days) to 1,500 mg sulfadoxine and 75 mg pyrimethamine for the treatment o...

show abstract

Bioequivalence assessment of Azomycin® (Julphar, UAE) as compared to Zithromax® (Pfizer, USA)—two brands of azithromycin—in healthy human volunteers

Cited by 12 publications

References 21 publications

Pharmacokinetics and Bioequivalence of 2 Azithromycin Tablet Formulations: A Randomized, Open‐Label, 2‐Stage Crossover Study in Healthy Volunteers

Pharmacokinetics and Bioequivalence of 2 Azithromycin Tablet Formulations: A Randomized, Open‐Label, 2‐Stage Crossover Study in Healthy Volunteers

A Reference‐Scaled Average Bioequivalence Study of Azithromycin Tablets Manufactured in China and the United States: An Open‐Label, Randomized, Single‐Dose, 3‐Way Crossover Study in Healthy Chinese Subjects Under Fasted and Fed Conditions

Pharmacokinetics and Ex Vivo Antimalarial Activity of Artesunate-Azithromycin in Healthy Volunteers

Contact Info

Product

Resources

About