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J Pharm Sci. 2016 Mar;105(3):1295-300. doi: 10.1016/j.xphs.2015.12.003. Epub 2016 Jan 30.

Do We Bury Antibacterials When Launching? Cefaclor Example.

Author information

1
Department of Pharmacology and Toxicology, Faculty of Medicine Novi Sad, University of Novi Sad, 21000 Novi Sad, Serbia.
2
Department of Pharmacology and Toxicology, Faculty of Medicine Novi Sad, University of Novi Sad, 21000 Novi Sad, Serbia. Electronic address: aanaa_tomas@yahoo.com.
3
Institute of Emergency Medicine, Clinical Center of Vojvodina, 21000 Novi Sad, Serbia.

Abstract

This study aimed to compare existing dosing regimens of cefaclor with recommended pharmacokinetic/pharmacodynamic (PK/PD) parameters and to see if the proposed dosing regimen could have been the reason for development of bacterial resistance. PKs of cefaclor were determined after administrating the highest therapeutic dose of 750 mg in standard release (SF) and modified release form (MRF) in 12 volunteers. The study was performed on clinical isolates of the most frequent causative agents in urinary and respiratory infections. Minimum inhibitory concentration (MIC), postantibiotic effect, and PK/PD efficacy indices were determined. Peak plasma concentrations of 23.142 ± 5.67 (SF) and 8.7 ± 2.09 μg/mL (MRF) were observed after 40-60 min and 3.04 ± 0.75 h, respectively. MIC for investigated bacterial strains ranged from 1 to 4 mg/L. Postantibiotic effect lasted from 2.10-2.18 ± 0.2 h for Gram-positive to 0.58-0.90 ± 0.05 h for Gram-negative bacteria. PK/PD indices (t > MIC) ranged from 27.08 ± 5.93% to 43.23 ± 6.54% of 8-h dosing interval (SF) and 22.57 ± 8.93% to 49.65 ± 1.95% of 12-h dosing interval (MRF). Plasma levels were below MIC for more than 50% of the dosing interval even for the most sensitive pathogens (MIC = 1 mg/L). During both dosing intervals the total "antibacterial activity" was not longer than 6 h for Gram-positive and 5 h for Gram-negative bacteria for SF and 9 h for Gram-positive and 5 h for Gram-negative bacteria for MRF.

KEYWORDS:

drug design; formulation; pharmacodynamics; pharmacokinetics; pharmacokinetics/pharmacodynamics

PMID:
26886327
DOI:
10.1016/j.xphs.2015.12.003
[Indexed for MEDLINE]

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