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[Modification of ofloxacin pharmacokinetics induced by prolonged mechanical ventilation]
1Département d'Anesthésie-Réanimation, Hôpital Sainte-Marguerite, Marseille.
Abstract:
The pharmacokinetics of ofloxacin was studied in 12 intensive care patients, 6 of whom being under mechanical ventilation. All patients had a creatinine clearance greater than 60 ml/min/1.73 m2 and they were given 3 mg/kg. IV ofloxacin within 30 mn, with a twice daily regimen for 7 days. Pharmacokinetic studies were performed on day 1 (D1) and 7 (D7). Between D1 and D7 a significant increase in T 1/2 beta, AUC and blood levels were observed together with a decrease in total body clearance. Creatinine clearance was not modified between D1 and D7 but ofloxacin renal clearance was considerably altered. Abnormalities in ofloxacin renal tubular secretion may account for the drug cumulation which was observed during repeated administration in intensive care patients.
Insights
Repeated ofloxacin doses in intensive care patients led to increased drug levels and half-life, suggesting altered renal clearance. This indicates potential for ofloxacin accumulation in critically ill patients.
Area of Science:
- Pharmacology
- Clinical Pharmacy
- Critical Care Medicine
Context:
- Intensive care unit (ICU) patients often require broad-spectrum antibiotics like ofloxacin.
- Mechanical ventilation can influence drug pharmacokinetics.
- Understanding drug behavior in critically ill populations is crucial for safe and effective treatment.
Purpose:
- To investigate the pharmacokinetic changes of ofloxacin during a 7-day treatment course in intensive care patients.
- To assess the impact of repeated intravenous ofloxacin administration on drug levels, clearance, and half-life.
- To explore potential mechanisms for observed pharmacokinetic alterations, particularly related to renal function.
Summary:
- Twelve intensive care patients received intravenous ofloxacin (3 mg/kg twice daily for 7 days).
- Pharmacokinetic studies on Day 1 and Day 7 revealed a significant increase in ofloxacin's terminal half-life (T 1/2 beta) and area under the curve (AUC).
- Total body clearance decreased, while renal clearance was significantly altered, despite stable creatinine clearance, suggesting impaired tubular secretion contributes to drug accumulation.
Impact:
- Findings highlight the potential for ofloxacin accumulation in intensive care patients with repeated dosing.
- Altered renal tubular secretion is implicated as a key factor in the observed drug cumulation.
- This research informs therapeutic drug monitoring and dosing adjustments for ofloxacin in critically ill populations.