Ofloxacin pharmacokinetics in mechanically ventilated patients

The pharmacokinetics of ofloxacin were studied in 12 intensive care patients, 6 of whom were under controlled mechanical ventilation. All patients had a creatinine clearance of greater than 80 ml/min per 1.73 m2. They were given 3 mg of ofloxacin per kg of body weight intravenously at a constant flow rate in 30 min twice a day for 7 days. Pharmacokinetic studies were performed on days 1 and 7. Between days 1 and 7, significant increases in the alpha (distribution) and beta (elimination) phase half-lives, the area under the serum concentration-time curve, and peak and trough levels in serum were observed, together with a marked decrease (greater than 50%) in total body clearance. Possible contributing factors for alteration of ofloxacin pharmacokinetics in ventilated patients were patient age, liver dysfunction, drug interaction, and drug accumulation in a deep compartment. This study shows that in intensive care patients the pharmacokinetics of ofloxacin differ from those reported for healthy volunteers.