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Chapter 7 : Drug-Drug Interactions

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Abstract:

Pharmacokinetic drug-drug interactions occur when the absorption, metabolism, distribution, or elimination of one drug is altered by coadministration of another. Compared with many antimicrobial drugs, the fluoroquinolones cause relatively few pharmacokinetic drug-drug interactions. Absorption interactions are the most important, and the absorption of all fluoroquinolones is reduced when they are given with multivalent cations, including those frequently found in antacids such as aluminum, magnesium, and calcium. This chapter reviews fluoroquinolone pharmacokinetic drug-drug interactions, with an emphasis on newer agents, and discusses some remaining controversial issues. The current prescribing information for each fluoroquinolone should be consulted for the most recent drug-drug interaction information. Similar to the quinolone warfarin interaction, several early case reports suggested that quinolones may impair the metabolism of cyclosporine and promote nephrotoxicity. Though rifampin is one of the most potent inducers known of multiple P450 enzymes, there appears to be little effect on metabolism of most quinolones. Research has focused on the neuroinhibitory effects of quinolones, on gamma amino butyric acid receptors, central nervous system (CNS) adverse effects of the fluoroquinolones, and a possible pharmacodynamic interaction with certain nonsteroidal anti-inflammatory drugs (NSAIDs).

Citation: Qaqish R, Polk R. 2003. Drug-Drug Interactions, p 133-146. In Hooper D, Rubinstein E (ed), Quinolone Antimicrobial Agents, Third Edition. ASM Press, Washington, DC. doi: 10.1128/9781555817817.ch7
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Figure 1

Proposed mechanism by which metal (Me ) cations chelate fluoroquinolones.

Citation: Qaqish R, Polk R. 2003. Drug-Drug Interactions, p 133-146. In Hooper D, Rubinstein E (ed), Quinolone Antimicrobial Agents, Third Edition. ASM Press, Washington, DC. doi: 10.1128/9781555817817.ch7
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Figure 2

Effects of Maalox and ranitidine on absorption of moxifloxacin. Data from reference .

Citation: Qaqish R, Polk R. 2003. Drug-Drug Interactions, p 133-146. In Hooper D, Rubinstein E (ed), Quinolone Antimicrobial Agents, Third Edition. ASM Press, Washington, DC. doi: 10.1128/9781555817817.ch7
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Figure 3

Effects of didanosine table formulation on absorption of ciprofloxacin. Reprinted from reference with permission.

Citation: Qaqish R, Polk R. 2003. Drug-Drug Interactions, p 133-146. In Hooper D, Rubinstein E (ed), Quinolone Antimicrobial Agents, Third Edition. ASM Press, Washington, DC. doi: 10.1128/9781555817817.ch7
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Figure 4

Effects of clinafloxacin on clearance of theophylline (a) and caffeine (b). Reprinted from reference with permission.

Citation: Qaqish R, Polk R. 2003. Drug-Drug Interactions, p 133-146. In Hooper D, Rubinstein E (ed), Quinolone Antimicrobial Agents, Third Edition. ASM Press, Washington, DC. doi: 10.1128/9781555817817.ch7
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Tables

Generic image for table
Table 1

Substrates, inducers, and inhibitors of the CYP450 isoenzymesª

Citation: Qaqish R, Polk R. 2003. Drug-Drug Interactions, p 133-146. In Hooper D, Rubinstein E (ed), Quinolone Antimicrobial Agents, Third Edition. ASM Press, Washington, DC. doi: 10.1128/9781555817817.ch7
Generic image for table
Table 2

Pharmacokinetic absorption interactions between cations and fluoroquinolones

Citation: Qaqish R, Polk R. 2003. Drug-Drug Interactions, p 133-146. In Hooper D, Rubinstein E (ed), Quinolone Antimicrobial Agents, Third Edition. ASM Press, Washington, DC. doi: 10.1128/9781555817817.ch7
Generic image for table
Table 3

Summary of fluoroquinolone-methylxanthine interactionsª

Citation: Qaqish R, Polk R. 2003. Drug-Drug Interactions, p 133-146. In Hooper D, Rubinstein E (ed), Quinolone Antimicrobial Agents, Third Edition. ASM Press, Washington, DC. doi: 10.1128/9781555817817.ch7
Generic image for table
Table 4

Summary of warfarin-fluoroquinolone interactionsª

Citation: Qaqish R, Polk R. 2003. Drug-Drug Interactions, p 133-146. In Hooper D, Rubinstein E (ed), Quinolone Antimicrobial Agents, Third Edition. ASM Press, Washington, DC. doi: 10.1128/9781555817817.ch7

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