Info

3,018

Data are taken from Ross, D. L., and Riley, C. M.: J. Pharm. Biomed. Anal. 12: 1325, 1994.

"Each value represents an average of literature values.

Data are taken from Ross, D. L., and Riley, C. M.: J. Pharm. Biomed. Anal. 12: 1325, 1994.

"Each value represents an average of literature values.

more basic nitrogen atom of the piperazino group fall in the range of 8.1 to 9.3 (Table 6.6).62 At most physiologically relevant pH values, significant dissociation of both the 3-carboxylic acid and the basic 7-(1-piperazino) groups occurs, leading to significant fractions of zwitterionic species. As an example, the dissociation equilibria for norfloxacin are illustrated in Figure 6.6.62,63

The tendency for certain fluoroquinolones (e.g., norfloxacin, ciprofloxacin) in high doses to cause crystalluria in alkaline urine is, in part, caused by the predominance of the comparatively less soluble zwitterionic form. Solubility data presented for ofloxacin in the 15th edition of the USP dramatically illustrate the effect of pH on water solubility of compounds of the fluoroquinolone class. Thus, the solubility of ofloxacin in water is 60 mg/mL at pH values ranging from 2 to 5, falls to 4 mg/mL at pH 7 (near the isoelectric point, pI), and rises to 303 mg/mL at pH 9.8.

The excellent chelating properties of the quinolones provide the basis for their incompatibility with antacids, hematinics, and mineral supplements containing divalent or trivalent metals. The quinolones may form 1:1, 2:1, or 3:1 chelates with metal ions such as Ca+2, Mg+2, Zn+2, Fe+2, Fe+3, and Bi+3. The stoichiometry of the chelate formed depends on various factors, such as the relative concentrations of chelating agent (quinolone) and metal ion present, the valence (or charge) on the metal ion, and the pH. Since such chelates are often insoluble in water, coincidental oral administration of a quinolone with an antacid, a hematinic, or a mineral supplement can significantly reduce the oral bioavailability of the quinolone. As an example, the insoluble 2:1 chelate formed between ciprofloxacin and magnesium ion is shown in Figure 6.7. The presence of divalent ions (such as Mg+2) in the urine may also contribute to the comparatively lower solubility of certain fluoroquinolones in urine than in plasma.

Nalidixic Acid

1-Ethyl-1,4-dihydro-7-methyl-4-oxo-1,8-naphthyridine-3-carboxylic acid (NegGram) occurs as a pale buff crystalline

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