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Chapter 6 : Pharmacokinetics of Fluoroquinolones

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Abstract:

This chapter reviews important aspects of the pharmacokinetic properties of fluoroquinolones. Fluoroquinolones are generally well absorbed after oral administration. In general, food may delay the onset but not the extent of absorption of fluoroquinolones. The piperazine ring at the C-7 appears to be the major site for biotransformation of most fluoroquinolones; the extent and rate of biotransformation can be modulated by substitutions on the ring. Grepafloxacin pharmacokinetics varied slightly among men and women volunteers, but the differences were shown to be attributable to differences in lean or total body weight. In view of its potency against , ciprofloxacin has been the most extensively studied agent in patients with cystic fibrosis. There was no effect of sex, age, or race on gatifloxacin pharmacokinetics. Grepafloxacin populations pharmacokinetics was studied in 76 patients with acute bacterial exacerbations of chronic bronchitis to assess factors associated with efficacy in these patients. However, age, gender, and dose were not found to be significant predictors of grepafloxacin pharmacokinetics. In view of the usefulness of several fluoroquinolones for opportunistic as well a traditional pathogens, the oral bioavailability and pharmacokinetics of several agents have been studied in this patient group. Recent advances in the understanding of the pathogenesis and structure-activity relationships for fluoroquinolone-induced bone and cartilage toxicity has fostered the investigation of the pharmacokinetics of newer agents with improved activity against gram-positive bacteria in children. Pharmacokinetics and dosage adjustment of selected fluoroquinolones in renal impairment are discussed in the chapter.

Citation: Dudley M. 2003. Pharmacokinetics of Fluoroquinolones, p 115-132. In Hooper D, Rubinstein E (ed), Quinolone Antimicrobial Agents, Third Edition. ASM Press, Washington, DC. doi: 10.1128/9781555817817.ch6
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Figure 1

Chemical structures of selected fluoroquinolones.

Citation: Dudley M. 2003. Pharmacokinetics of Fluoroquinolones, p 115-132. In Hooper D, Rubinstein E (ed), Quinolone Antimicrobial Agents, Third Edition. ASM Press, Washington, DC. doi: 10.1128/9781555817817.ch6
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Image of Figure 2
Figure 2

Comparison of fluoroquinolone concentrations in 12 healthy volunteers in a crossover study. Solid lines, dn = dose normalized values. Reprinted from reference 44 with permission.

Citation: Dudley M. 2003. Pharmacokinetics of Fluoroquinolones, p 115-132. In Hooper D, Rubinstein E (ed), Quinolone Antimicrobial Agents, Third Edition. ASM Press, Washington, DC. doi: 10.1128/9781555817817.ch6
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Tables

Generic image for table
Table 1

Summary of the pharmacokinetics of fluoroquinolones following a single dose in normal human volunteers

Citation: Dudley M. 2003. Pharmacokinetics of Fluoroquinolones, p 115-132. In Hooper D, Rubinstein E (ed), Quinolone Antimicrobial Agents, Third Edition. ASM Press, Washington, DC. doi: 10.1128/9781555817817.ch6
Generic image for table
Table 2

Pharmacokinetics of fluoroquinolones in serum and cantharides-induced blister fluids in normal volunteers

Citation: Dudley M. 2003. Pharmacokinetics of Fluoroquinolones, p 115-132. In Hooper D, Rubinstein E (ed), Quinolone Antimicrobial Agents, Third Edition. ASM Press, Washington, DC. doi: 10.1128/9781555817817.ch6
Generic image for table
Table 3

Pharmacokinetic parameters for six fluoroquinolones tested in 12 volunteers

Citation: Dudley M. 2003. Pharmacokinetics of Fluoroquinolones, p 115-132. In Hooper D, Rubinstein E (ed), Quinolone Antimicrobial Agents, Third Edition. ASM Press, Washington, DC. doi: 10.1128/9781555817817.ch6
Generic image for table
Table 4

Comparison of pharmacokinetics of ciprofloxacin in cystic fibrosis patients

Citation: Dudley M. 2003. Pharmacokinetics of Fluoroquinolones, p 115-132. In Hooper D, Rubinstein E (ed), Quinolone Antimicrobial Agents, Third Edition. ASM Press, Washington, DC. doi: 10.1128/9781555817817.ch6
Generic image for table
Table 5

Pharmacokinetics and dosage adjustment of selected fluoroquinolones in renal impairment

Citation: Dudley M. 2003. Pharmacokinetics of Fluoroquinolones, p 115-132. In Hooper D, Rubinstein E (ed), Quinolone Antimicrobial Agents, Third Edition. ASM Press, Washington, DC. doi: 10.1128/9781555817817.ch6

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