Page 852 - Basic _ Clinical Pharmacology ( PDFDrive )

838 SECTION VIII Chemotherapeutic Drugs

O O
COOH F COOH

CH 3 N N HN N N

C 2 H 5
C 2 H 5
Nalidixic acid Norfloxacin
O O
F COOH F COOH

HN N N CH 3 N N N
O
CH 3
Ciprofloxacin Levofloxacin

O
O
F F COOH
CH 2 O F F CO 2 H
H N N
N N N
O N N
H 3 C H 2 N
Moxifloxacin Gemifloxacin

FIGURE 46–3 Structures of nalidixic acid and some fluoroquinolones.

versus Gram-positive species is useful for differentiating these typically used in combination with a second active agent, such
agents. Norfloxacin, which is no longer available in the USA, as rifampin, to prevent emergence of resistance while on therapy.
is the least active of the fluoroquinolones against both Gram- Enterococci tend to be less susceptible than staphylococci, limit-
negative and Gram-positive organisms, with minimum inhibitory ing the efficacy of fluoroquinolones in infections caused by these
concentrations (MICs) fourfold to eightfold higher than those organisms. Ciprofloxacin is the most active agent of this group
of ciprofloxacin. Ciprofloxacin, enoxacin, lomefloxacin, levo- against Gram-negative organisms, particularly P aeruginosa. Levo-
floxacin, ofloxacin, and pefloxacin comprise a second group floxacin, the l-isomer of ofloxacin, has superior activity against
of similar agents possessing excellent Gram-negative activity and Gram-positive organisms, especially Streptococcus pneumoniae.
moderate to good activity against Gram-positive bacteria. Cip- Gatifloxacin, gemifloxacin, and moxifloxacin make up a third
rofloxacin and levofloxacin are the two agents from this group group of fluoroquinolones with improved activity against Gram-
that are used systemically in the USA. MICs for Gram-negative positive organisms, particularly S pneumoniae and some staphylo-
cocci and bacilli, including Enterobacter sp, P aeruginosa, Neis- cocci. Gemifloxacin is active in vitro against ciprofloxacin-resistant
seria meningitidis, Haemophilus sp, and Campylobacter jejuni, are strains of S pneumoniae, but in vivo efficacy is unproven. Although
1–2 mcg/mL and often less. Methicillin-susceptible strains of S MICs of these agents for staphylococci are lower than those of cip-
aureus are generally susceptible to these fluoroquinolones, but rofloxacin (and the other compounds mentioned in the paragraph
methicillin-resistant strains of staphylococci are often resistant. above), it is not known whether the enhanced activity is sufficient
When treating staphylococcal infections, fluoroquinolones are to permit use of these agents for treatment of infections caused by

TABLE 46–1 Pharmacokinetic properties of some fluoroquinolones.

Oral Peak Serum Primary Route of
Drug Half-Life (h) Bioavailability (%) Concentration (mcg/mL) Oral Dose (mg) Excretion
Ciprofloxacin 3–5 70 2.4 500 twice daily Renal
Gemifloxacin 8 70 1.6 320 once daily Renal and nonrenal
Levofloxacin 5–7 95 5.7 500 once daily Renal
Moxifloxacin 9–10 >85 3.1 400 once daily Nonrenal
Norfloxacin 3.5–5 80 1.5 400 twice daily Renal
Ofloxacin 5–7 95 2.9 400 twice daily Renal