Effect of Food on the Bioavailability of Omadacycline in Healthy Participants

Tzanis, Evan; Manley, Amy; Villano, Stephen; Tanaka, Sébastien; Bai, Stephen A.; Loh, Evan

doi:10.1002/jcph.814

Cited by 37 publications

(34 citation statements)

References 11 publications

(26 reference statements)

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“…Protein binding for KBP-7072 was approximately 75% in animal and human plasma. This compares with >80% for eravacycline, 19 approximately 20% for omadacycline, 16,18 and 71% to 89% for tigecycline when assessed in animal plasma. 20 Bioavailability with KBP-7072 ranged from 19% to 28% compared with 22.6% in a rat model with omadacycline.…”

Section: Discussionmentioning

confidence: 83%

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Nonclinical Pharmacokinetics, Protein Binding, and Elimination of KBP-7072, an Aminomethylcycline Antibiotic, in Animal Models

Tan

Zhang

Liu

et al. 2020

Antimicrob Agents Chemother

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KBP-7072 is a semisynthetic aminomethylcycline with broad-spectrum activity against Gram-positive and Gram-negative pathogens, including multidrug-resistant bacterial strains. The pharmacokinetics (PK) of KBP-7072 after oral and intravenous (i.v.) administrations of single and multiple doses were investigated in animal models, including during fed and fasted states, and the protein binding and excretion characteristics were also evaluated. In Sprague-Dawley (SD) rats, beagle dogs, and CD-1 mice, KBP-7072 demonstrated a linear PK profile after the administration of single oral and i.v. and multiple oral doses. The oral bioavailability ranged from 12% to 32%. The mean time to maximum concentration (Tmax) ranged from 0.5 to 4 h, and the mean half-life ranged from approximately 6 to 11 h. The administration of oral doses in the fed state resulted in marked reductions in the maximum plasma concentration (Cmax) and the area under the concentration-time curve (AUC) compared with dosing in fasted animals. The mean bound fractions of KBP-7072 were 77.5%, 69.8%, 64.5%, 69.3%, and 69.2% in mouse, rat, dog, monkey, and human plasma, respectively. Following a single 22.5-mg/kg oral dose of KBP-7072 in SD rats, the cumulative excretion in feces was 64% and that in urine was 2.5% of the administered dose. The PK results in animal models are consistent with single- and multiple-ascending-dose studies in healthy volunteers and confirm the suitability of KBP-7072 for once-daily oral and i.v. administration in clinical studies.

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Section: Discussionmentioning

confidence: 83%

“…15,16 This is consistent with results from oral administration of omadacycline where dosing with food markedly reduced systemic exposure. 18 It is important to investigate the effect of antibiotics on the gut microbiota.…”

Section: Discussionmentioning

confidence: 99%

Nonclinical Pharmacokinetics, Protein Binding, and Elimination of KBP-7072, an Aminomethylcycline Antibiotic, in Animal Models

Tan

Zhang

Liu

et al. 2020

Antimicrob Agents Chemother

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“…A Phase I, random-sequence, open-label, 4-period crossover study evaluated the effects of food on the pharmacokinetics of omadacycline in healthy subjects (Tzanis et al, 2016) [24]. In each period subjects received a single 300 mg oral dose of omadacycline but the meal time varied relative to dosing: A) ≥6-h fast before dosing, B) standard, high fat, non-dairy meal 4 h before dosing, C) standard, high fat, non-dairy meal 2 h before dosing, and D) standard, high fat meal containing dairy 2 h before dosing.…”

Section: • • Food Effectmentioning

confidence: 99%

Omadacycline: Development of a Novel Aminomethylcycline Antibiotic for Treating Drug-Resistant Bacterial Infections

2016

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Omadacycline is a first-in-class aminomethylcycline antibiotic that circumvents common tetracycline resistance mechanisms. In vitro omadacycline has potent activity against Gram-positive aerobic bacteria including methicillin-resistant Staphylococcus aureus, penicillin-resistant and multidrug-resistant Streptococcus pneumoniae, and vancomycin-resistant Enterococcus spp. It is also active against common Gram-negative aerobes, some anaerobes and atypical bacteria including Legionella spp. and Chlamydia spp. Ongoing Phase III clinical trials with omadacycline are investigating once daily doses of 100 mg intravenously followed by once-daily doses of 300 mg orally for the treatment of acute bacterial skin and skin structure infections and community-acquired bacterial pneumonia. This paper provides an overview of the microbiology, nonclinical evaluations, clinical pharmacology and initial clinical experience with omadacycline.

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“…Omadacycline is being developed for both intravenous (i.v.) and oral administration ( 1 , 10 – 13 ). Phase 3 human clinical trials with omadacycline as monotherapy for the treatment of acute bacterial skin and skin structure infections (ClinicalTrials.gov registration no.…”

Section: Introductionmentioning

confidence: 99%

Comparison of Omadacycline and Tigecycline Pharmacokinetics in the Plasma, Epithelial Lining Fluid, and Alveolar Cells of Healthy Adult Subjects

Gotfried

Horn

Garrity-Ryan

et al. 2017

Antimicrob Agents Chemother

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The steady-state concentrations of omadacycline and tigecycline in the plasma, epithelial lining fluid (ELF), and alveolar cells (AC) of 58 healthy adult subjects were obtained. Subjects were administered either omadacycline at 100 mg intravenously (i.v.) every 12 h for two doses followed by 100 mg i.v. every 24 h for three doses or tigecycline at an initial dose of 100 mg i.v. followed by 50 mg i.v. every 12 h for six doses. A bronchoscopy and bronchoalveolar lavage were performed once in each subject following the start of the fifth dose of omadacycline at 0.5, 1, 2, 4, 8, 12, or 24 h and after the start of the seventh dose of tigecycline at 2, 4, 6, or 12 h. The value of the area under the concentration-time curve (AUC) from time zero to 24 h postdosing (AUC0–24) (based on mean concentrations) in ELF and the ratio of the ELF to total plasma omadacycline concentration based on AUC0–24 values were 17.23 mg · h/liter and 1.47, respectively. The AUC0–24 value in AC was 302.46 mg · h/liter, and the ratio of the AC to total plasma omadacycline concentration was 25.8. In comparison, the values of the AUC from time zero to 12 h postdosing (AUC0–12) based on the mean concentrations of tigecycline in ELF and AC were 3.16 and 38.50 mg · h/liter, respectively. The ratio of the ELF and AC to total plasma concentrations of tigecycline based on AUC0–12 values were 1.71 and 20.8, respectively. The pharmacokinetic advantages of higher and sustained concentrations of omadacycline compared to those of tigecycline in plasma, ELF, and AC suggest that omadacycline is a promising antibacterial agent for the treatment of lower respiratory tract bacterial infections caused by susceptible pathogens.

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Effect of Food on the Bioavailability of Omadacycline in Healthy Participants

Cited by 37 publications

References 11 publications

Nonclinical Pharmacokinetics, Protein Binding, and Elimination of KBP-7072, an Aminomethylcycline Antibiotic, in Animal Models

Nonclinical Pharmacokinetics, Protein Binding, and Elimination of KBP-7072, an Aminomethylcycline Antibiotic, in Animal Models

Omadacycline: Development of a Novel Aminomethylcycline Antibiotic for Treating Drug-Resistant Bacterial Infections

Comparison of Omadacycline and Tigecycline Pharmacokinetics in the Plasma, Epithelial Lining Fluid, and Alveolar Cells of Healthy Adult Subjects

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