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

Abstract

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.

Omadacycline Enters the Ring: A New Antimicrobial Contender

“…In a phase I assessment of 58 healthy adult subjects, omadacycline and tigecycline plasma, ELF, and alveolar cell concentrations were compared. 22 Systemic exposure, based upon AUC 0-24 and AUC 0-12 values, was 3-fold higher in the plasma, ELF, and alveolar cells for omadacycline versus tigecycline. There are no currently published data on omadacycline pharmacodynamics against gram-negative organisms.…”

“…Finally, omadacycline penetrated well into the epithelial lining fluid (ELF), suggesting that this agent may be an option for treatment of lower respiratory tract bacterial infections. In a phase I assessment of 58 healthy adult subjects, omadacycline and tigecycline plasma, ELF, and alveolar cell concentrations were compared . Systemic exposure, based upon AUC 0–24 and AUC 0–12 values, was 3‐fold higher in the plasma, ELF, and alveolar cells for omadacycline versus tigecycline.…”

Monitoring Antibiotics and Inflammatory Markers in Human Blood: Impact in Choice of Antibiotic Therapy and Used Methods

“…The values of the minimum inhibitory concentrations during antibiotic therapy with the main currently known tetracyclines are shown in Table 4. Gotfried et al [89] studied the pharmacokinetics of tetracyclines and the achievement of working concentrations in blood plasma and alveolar fluid, during the treatment of bacterial infections of the respiratory tract. Since the half-life of tetracyclines, according to their pharmacokinetic parameters, comprises many hours (Table 5), the dosage of the drugs and the values of the minimum inhibitory concentrations differ from the data for beta-lactams.…”

“…Pharmacokinetic parameters for omadacycline and tigecycline in plasma, administered intravenously for 30 min, at doses of 100 mg and 50 mg, respectively[89] …”

In Vitro and Intracellular Activities of Omadacycline against Legionella pneumophila

“…2). Combining the observed MIEC values at day 5 with the observed mean epithelial lining fluid (ELF) the area under the concentration-time curve from 0 to 24 h (AUC 0 -24 ) value (17.23 mg · h/liter) and the observed mean alveolar cell (AC) AUC 0 -24 value (302.42 mg · h/l) (24), the estimated AUC 0 -24 /MIEC ratio in ELF and AC would be ϳ143 and ϳ2,520 for tested strains of L. pneumophila, respectively. These important intracellular findings suggest an achievable level of omadacycline at the infection site and support the potency and clinical efficacy of omadacycline for the treatment of CABP caused by susceptible strains of L. pneumophila.…”