Bioavailability is more than 90%. T max is 1 to 2 h.
Apparent Vd is 0.65 L/kg, and it is 11% to 12% protein bound. Ratio of tissue (fluid) concentrations to concurrent plasma concentrations is as follows: CSF, 0.5 to 0.9; saliva, 1; sputum, 1; blister fluid, 1; urine, 10; normal skin, 10; nails, 1; blister skin, 2; vaginal tissue, 1; and vaginal fluid, 0.4 to 0.7.
Mean body Cl is 0.23 mL/min/kg; t ½ is 20 to 50 h. The drug is cleared primarily by renal excretion, about 80% in urine as unchanged drug and 11% excreted in urine as metabolites.
A 3-h session decreases plasma concentrations about 50%.
Renal Function Impairment
Pharmacokinetics are markedly affected; there is an inverse relationship between t ½ and CrCl.
9 mo to 15 yr of age
Mean Cl is 0.4 to 0.66 mL/min/kg; t ½ is 15.2 to 25 h. C max is 2.9 to 14.1 mcg/mL; Vd ss is 0.722 to 1.069.
Neonates (gestational age 26 to 29 wk)
Mean Cl is 0.18 to 0.333 mL/min/kg (increases with time after birth); t ½ is 73.6 to 46.6 h (decreases with time after birth).
Alfentanil, benzodiazepines (eg, midazolam), buspirone, corticosteroids (eg, prednisone), losartan, nisoldipine, sulfonylureas (eg, glyburide), tacrolimus, theophylline, tricyclic antidepressants, vinca alkaloids (eg, vincristine), zidovudine, zolpidem
Levels may be elevated by fluconazole, increasing the risk of adverse reactions and toxicity.
Anticoagulants (eg, warfarin)
Anticoagulant effect may be increased.
Cimetidine, rifamycins (eg, rifampin)
Fluconazole plasma levels may be reduced, decreasing therapeutic effects.
Contraindicated; increased cisapride plasma levels with cardiotoxicity may occur.
Increased cyclosporine concentrations.
Hydantoins (eg, phenytoin)
Increased hydantoin levels.
May increase fluconazole levels, increasing adverse reactions.