Current Updates in Pharmacokinetics and Pharmacodynamics of Fluoroquinolones

Young Hwii Ko; Phil Hyun Song

doi:10.14777/kjutii.2015.10.1.1

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Ko and Song: Current Updates in Pharmacokinetics and Pharmacodynamics of Fluoroquinolones

Review

Korean J Urogenit Tract Infect Inflamm 2015;10(1):1-6.

Published online: 17 December 2015

DOI: https://doi.org/10.14777/kjutii.2015.10.1.1

Current Updates in Pharmacokinetics and Pharmacodynamics of Fluoroquinolones

Young Hwii Ko, Phil Hyun Song

Department of Urology, Yeungnam University College of Medicine, Daegu, Korea

Correspondence to: Phil Hyun Song, http://orcid.org/0000-0002-3801-258X, Department of Urology, Yeungnam University College of Medicine, 170 Hyeonchung-ro, Nam-gu, Daegu 705-703, Korea Tel: +82-53-620-3693, Fax: +82-53-627-5535 E-mail: sph04@hanmail.net

Received 27 March 2014 Revised 13 April 2014 Accepted 13 April 2014

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

The ultimate goal of antimicrobial treatment is to decrease the morbidity and mortality related to infection. Maximizing these outcomes requires an understanding of the complex interactions between the drug administered, the host, and the infecting pathogen. Pharmacokinetics, which deals with the disposition of a drug in the body, focuses on such parameters as absorption, distribution, and elimination. Pharmacodynamics more specifically focuses on the interaction between the drug concentration at the site of action over time and the resulting antimicrobial effect. Use of quinolones has increased in vitro activity against several important pathogenic organisms as well as augmented pharmacokinetic parameters. These properties result in enhanced pharmacodynamic characteristics and should improve therapeutic outcomes against selected pathogens. In this article the pharmacokinetics and pharmacodynamic potential of these quinolones, particularly fluoroquinolones, is reviewed.

Keywords: Fluoroquinolones, Pharmacokinetics, Pharmacology

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Fig. 1.

The core quinolone nucleus.

Table 1.

Pharmacokinetic properties of fluoroquinolones

Fluoroquinolone	Oral dose (mg)	tmax (h)	Cmax (g/ml)	t1/2 (h)	AUC ([mg·h]/L)
Sparfloxacin	200	4.0	0.7	21.0	19.0
Levofloxacin	200	1.5	2.0	6.0	20.0
Grepafloxacin Trovafloxacin	200 200	2.1 0.7	0.7 2.9	11.0 7.8	8.8 24.0
Clinafloxacin	200	1.5	1.6	6.3	11.0

t_max: time after dosing for maximal concentration to be reached, Cmax: maximal serum concentration, t1/2 : elimination half-life, AUC: area under the serum concentration curve.

Table 2.

Inflammatory fluid penetration of fluoroquinolones

Parameter	Grepafloxacin (400 mg)	Levofloxacin (500 mg)	Sparfloxacin (400 mg)	Trovafloxacin (200 mg)
Serum
t_max (h)	2.0	1.2	2.7	0.75
Cmax (g/ml)	1.5	6.6	1.6	2.9
t1/2 (h)	5.2	8.0	18	7.8
AUC ([mg·h]/L)	12	53	32	24
Blister fluid
t_max (h)	4.8	3.7	5.0	4.0
Cmax (g/ml)	1.1	4.3	1.3	1.2
t1/2 (h)	13	8.0	20	7.1
AUC ([mg·h]/L)	22	54	37	15
Percentage penetration (blister fluid value/serum value)
Cmax	73	65	81	41
AUC	180	100	117	63

t_max: time after dosing for maximal concentration to be reached, Cmax: maximal serum concentration, t1/2 : elimination half-life, AUC: area under the serum concentration curve.

Table 3.

Pharmacokinetic and pharmacodynamic parameters in antibiotic therapy

Parameters
Mechanism of bacterial killing
Concentration-independent
Concentration-dependent
Three parameters correlating with outcome
T >MIC
Cmax:MIC
AUC:MIC

MIC: minimum inhibitory concentration, T >MIC: time that the drug concentration is above the MIC. Cmax: maximal serum concentration AUC: area under the serum concentration curve.

Table 4.

Pharmacodynamic parameters predictive of the outcome associated with various classes of antimicrobials

Parameter	Class of antimicrobial
T >MIC	Penicillin Cephalosporins
	Carbapenems
	Macrolides
Cmax:MIC	Aminoglycosides
	Fluoroquinolones
AUC₂₄:MIC	Fluoroquinolones Azalides
	Ketolides

MIC: minimum inhibitory concentration, T >MIC: time above the MIC, Cmax: maximal serum concentration, AUC₂₄: 24-h area under serum concentration curve.

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