Pharmacokinetic Disposition of Quinolones in Human Body Fluids and Tissues

Abstract

The unique pharmacokinetic properties as well as the body fluid and tissue penetration of quinolones are discussed.Quinolones are well absorbed from the gastrointestinal tract and are eliminated with considerable d{fJerences in their terminal half-lives. The major elimination pathways of quinolones are renal excretion and hepatic metabolism. Renally. these drugs undergo the potential excretion mechanisms (glomerular filtration. tubular secretion. reabsorption). In the liver. they are metabolised primarily by oxidation as well as by conjugative pathways. However. the metabolic pattern and extent of metabolism d{f!er significantly between individual agents.Alterations in the pharmacokinetic disposition of these agents in liver and renal failure as well as in elderly patients are observed as predicted from their excretion pattern. In addition. quinolones can interact with a number of other compounds at hepatic (e.g. with xanthine derivatives). renal (with probenecid) and gastrointestinal (with antacids) sites.The volume of distribution of quinolones is considerably higher than body volume. which suggests intracellular penetration. Studies on tissue penetration show that concentrations exceeding plasma levels are obtained in most tissues. The highest tissue/plasma concentration ratios are achieved in lung and kidney. whereas concentrations in fat are considerably lower than in plasma.Body fluid penetration is introduced as a new approach to evaluate distribution kinetics of quinolones. With the exception of those in nasal secretions and ejaculate. body flUid levels of these drugs rarely reach plasma levels. The body fluid penetration model allows for d{f!erentiation among individual agents. There is no apparent relationship between d{f!erences in body fluid penetration of quinolones and d{f!erences in volume of distribution. For the clinical use of these drugs it is important that the concentrations achieved in body fluids and tissues are sufficient to kill most pathogens. A discussion on the relationship between plasma and tissue levels and the MICs of quinolones is. however. beyond the scope of this article.

Effective monitoring of concentrations of ofloxacin in saliva of patients with chronic respiratory tract infections

“…On the other hand, the fluoroquinolone antibiotics have been demonstrated to show extensive distribution and good penetration of the extravascular compartment (8,15,18,19,21). This characteristic is probably due to their low protein binding, high lipophilicity, and relatively small molecular size.…”

Intestinal Ciprofloxacin Efflux: The Role of Breast Cancer Resistance Protein (ABCG2)

“…In agreement with this assessment, ciprofloxacin has been classified as a low-permeability compound (Volpe, 2004;Zakelj et al, 2006). In vivo it displays variable oral bioavailability of between 50 and 80% (Sörgel et al, 1989a). Ciprofloxacin plasma clearance in vivo is predominantly renal (Jaehde et al, 1989;Rohwedder et al, 1990), but it is also subject to intestinal elimination (Sörgel et al, 1989b(Sörgel et al, , 1991 without undergoing significant metabolism (Sörgel et al, 1989b).…”

Quinolones: a class of antimicrobial agents

“…Penetration into the CNS is relatively good, and vitreous humor penetration is approximately 20% (Barza, 1991). Apart from nasal secretions (Dobbs et al, 1988) and ejaculate, body fluid concentrations of fluoroquinolones rarely reach plasma concentrations (Sorgel et al, 1989). Thus, the high tissue concentrations are a result of sequestration onto, or within, cells or cellular components of a tissue, although Carlier et al (1990) found no specific subcellular structure affinity to pefloxacin.…”