生物学的同等性とバイオアベイラビリティのジャーナル

概要

Pharmacokinetics and Bioequivalence Comparison of 600 mg Single-Dose Linezolid Oral Suspension and Tablet Formulation in Healthy Chinese Subjects

Ehab A H Abu-Basha, Ronette Gehring, Ahmad F Al-Shunnaq and Saad M Gharaibeh

Study background:Linezolid is indicated for the treatment of infections caused by aerobic Gram-positive bacteria. An oral suspension formulation poses an alternative to solid oral formulations in patients with swallowing difficulties, especially pediatric and geriatric patients, or patients with feeding tubes. Methods: This randomized, open-label, two-way cross-over, clinical pharmacology study in healthy Chinese male subjects evaluated the bioequivalence of single-dose 600 mg linezolid oral suspension to single-dose 600 mg linezolid film-coated tablet under fasted conditions. Pharmacokinetic blood sampling was carried out at various time points within 48 h post-dosing and plasma samples were analyzed using a validated high-performance liquid chromatography tandem mass spectrometric method. The primary endpoints were area under plasma concentration– time curve (AUC) from time zero to the time of the last quantifiable concentration (AUClast) and maximum plasma concentration (Cmax)for linezolid. Results: All 20 enrolled male subjects completed the study (mean age 25 years, mean body mass index 22 kg/ m2). The 90% confidence intervals (CIs) for the ratios of the adjusted geometric means of the primary endpoints, AUClast(97.81% [90% CI, 93.11-102.75%])and Cmax (113.67% [90% CI, 105.26-122.75%]), for the oral suspension formulation compared with the oral tablet were fullywithin the established bioequivalence limits of 80-125%. The two linezolid formulations were well tolerated and no serious adverse event or other significant adverse event was noted. Conclusions: Based on the results of this study, linezolid 600 mg oral suspension and linezolid 600 mg tablets are anticipated to be therapeutically equivalent and could be switched in subjects without any need for dose modification. Both formulations were safe and well tolerated.