Metabolism: Four metabolites have been identified in human urine which together account for approximately 15% of an oral dose. The metabolites have antimicrobial activity, but are less active than unchanged ciprofloxacin. Ciprofloxacin is an inhibitor of human cytochrome P450 1A2 (CYP1A2) mediated metabolism. Coadministration of ciprofloxacin with other drugs primarily metabolized by CYP1A2 results in increased plasma concentrations of these drugs and could lead to clinically significant adverse events of the coadministered drug (see CONTRAINDICATIONS; WARNINGS; PRECAUTIONS: DRUG INTERACTIONS).

Excretion: The serum elimination half-life in subjects with normal renal function is approximately 4 hours. Approximately 40 to 50% of an orally administered dose is excreted in the urine as unchanged drug. After a 250 mg oral dose, urine concentrations of ciprofloxacin usually exceed 200 µg/mL during the first two hours and are approximately 30 µg/mL at 8 to 12 hours after dosing. The urinary excretion of ciprofloxacin is virtually complete within 24 hours after dosing. The renal clearance of ciprofloxacin, which is approximately 300 mL/minute, exceeds the normal glomerular filtration rate of 120 mL/minute. Thus, active tubular secretion would seem to play a significant role in its elimination. Co-administration of probenecid with ciprofloxacin results in about a 50% reduction in the ciprofloxacin renal clearance and a 50% increase in its concentration in the systemic circulation. Although bile concentrations of ciprofloxacin are several fold higher than serum concentrations after oral dosing, only a small amount of the dose administered is recovered from the bile as unchanged drug. An additional 1 to 2% of the dose is recovered from the bile in the form of metabolites. Approximately 20 to 35% of an oral dose is recovered from the feces within 5 days after dosing. This may arise from either biliary clearance or transintestinal elimination.

With oral administration, a 500 mg dose, given as 10 mL of the 5% CIPRO Suspension (containing 250 mg ciprofloxacin/5mL) is bioequivalent to the 500 mg tablet. A 10 mL volume of the 5% CIPRO Suspension (containing 250 mg ciprofloxacin/5mL) is bioequivalent to a 5 mL volume of the 10% CIPRO Suspension (containing 500 mg ciprofloxacin/5mL).

Drug-drug Interactions: When CIPRO Tablet is given concomitantly with food, there is a delay in the absorption of the drug, resulting in peak concentrations that occur closer to 2 hours after dosing rather than 1 hour whereas there is no delay observed when CIPRO Suspension is given with food. The overall absorption of CIPRO Tablet or CIPRO Suspension, however, is not substantially affected. The pharmacokinetics of ciprofloxacin given as the suspension are also not affected by food. Concurrent administration of antacids containing magnesium hydroxide or aluminum hydroxide may reduce the bioavailability of ciprofloxacin by as much as 90%. (See PRECAUTIONS) The serum concentrations of ciprofloxacin and metronidazole were not altered when these two drugs were given concomitantly.

Concomitant administration with tizanidine is contraindicated (See CONTRAINDICATIONS). Concomitant administration of ciprofloxacin with theophylline decreases the clearance of theophylline resulting in elevated serum theophylline levels and increased risk of a patient developing CNS or other adverse reactions. Ciprofloxacin also decreases caffeine clearance and inhibits the formation of paraxanthine after caffeine administration. (See WARNINGS: PRECAUTIONS.) Special Populations: Pharmacokinetic studies of the oral (single dose) and intravenous (single and multiple dose) forms of ciprofloxacin indicate that plasma concentrations of ciprofloxacin are higher in elderly subjects ( > 65 years) as compared to young adults. Although the Cmax is increased 16-40%, the increase in mean AUC is approximately 30%, and can be at least partially attributed to decreased renal clearance in the elderly. Elimination half-life is only slightly (~20%) prolonged in the elderly. These differences are not considered clinically significant. (See PRECAUTIONS: Geriatric Use.)

In patients with reduced renal function, the half-life of ciprofloxacin is slightly prolonged. Dosage adjustments may be required. (See DOSAGE AND ADMINISTRATION.) In preliminary studies in patients with stable chronic liver cirrhosis, no significant changes in ciprofloxacin pharmacokinetics have been observed. The kinetics of ciprofloxacin in patients with acute hepatic insufficiency, however, have not been fully elucidated.

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