Pharmacokinetics of teicoplanin during continuous hemofiltration with a new and a 24-h used highly permeable membrane: rationale for therapeutic drug monitoring-guided dosage.

OBJECTIVE: Continuous venovenous hemofiltration (CVVH) is widely used in the management of critically ill patients, but only few administration guidelines for antimicrobial drugs are available. It is unclear whether the use of a filter for more than 24 hours might lead to less efficient extraction. This study describes the pharmacokinetics of teicoplanin during CVVH using a highly permeable membrane. METHODS: Pharmacokinetics of teicoplanin during continuous hemofiltration with a new (group 1) and a 24-h used (group 2), highly permeable polyamide membrane were assessed in 3 patients. RESULTS: The teicoplanin serum concentrations (44.0 +/- 18.5 mg/l vs 109.5 +/- 34.5 mg/l) and half-life of teicoplanin (4.6 +/- 1.1 h vs 5.2 +/- 0.7 h) differed significantly between the 2 groups indicating a smaller elimination of the drug on the second day. Substantial binding of teicoplanin to filter membranes could explain this observation. CONCLUSION: The results suggest that daily adjustment of the dosage is necessary to achieve sufficient teicoplanin concentrations and a fixed dosage recommendation is not suitable for this drug.

Soft tissue concentrations of ciprofloxacin in obese and lean subjects following weight-adjusted dosing.

OBJECTIVE: To investigate whether weight adjusted ciprofloxacin dosing results in comparable target site concentrations in obese and lean subjects. DESIGN: Comparative study in two populations. SUBJECTS: Twelve obese subjects (mean weight 122+/-22.6 kg, 28-52 y, male∶female ratio 4∶8) and 12 age- and sex-matched lean controls (mean weight 59+/-8.6 kg). METHODS: Sampling of interstitial space fluid by means of calibrated in vivo microdialysis after a weight-adjusted intravenous bolus dose of 2.85 mg/kg ciprofloxacin. Analysis of drug concentration by high pressure liquid chromatography. RESULTS: We found significantly higher peak and trough levels of ciprofloxacin in plasma for obese subjects (9.97+/-5.64 and 0.44+/-0.10 microg/ml vs 2.59+/-1.06 and 0.19+/-0.09 microg/ml in lean subjects, P<0.05), while concentration-time curves of interstitial fluid of muscle and subcutaneous fat did not differ between the groups. Tissue penetration, expressed as AUC(tissue)/AUC(plasma) ratio was significantly lower in obese subjects (0.45+/-0.27 vs 0.82+/-0.36, P<0.01). CONCLUSION: We conclude that the penetration process into the interstitial space fluid is impaired in obese subjects. Therefore antibiotic doses need not be adjusted for an increase in fat/water ratio. Weight-adjusted dosing based on actual body weight will yield adequate tissue levels for ciprofloxacin.

Continuous infusion versus intermittent administration of meropenem in critically ill patients.

This prospective crossover study compared the pharmacokinetics of meropenem by continuous infusion and by intermittent administration in critically ill patients. Fifteen patients were randomized to receive meropenem either as a 2 g iv loading dose, followed by a 3 g continuous infusion (CI) over 24 h, or by intermittent administration (IA) of 2 g iv every 8 h (q8h). Each regimen was followed for a period of 2 days, succeeded by crossover to the alternative regimen for the same period. Pharmacokinetic parameters (mean +/- SD) of CI included the following: concentration at steady state (Css) was 11.9+/-5.0 mg/L; area under the curve (AUC) was 117.5+/-12.9 mg/L x h. The maximum and minimum serum concentrations of meropenem (Cmax, Cmin) and total meropenem clearance (CItot) for IA were 110.1+/-6.9 mg/L, 8.5+/-1.0 mg/L and 9.4+/-1.2 L/h, respectively. The AUC during the IA regimen was larger than the AUC during CI (P < 0.001). In both treatment groups, meropenem serum concentrations remained above the MICs for the most common bacterial pathogens. We conclude that CI of meropenem is equivalent to the IA regimen and is therefore suitable for treating critically ill patients. Further studies are necessary to compare the clinical effects of CI and IA in this patient group.

Single-dose pharmacokinetics of meropenem during continuous venovenous hemofiltration.

The pharmacokinetic properties of meropenem were investigated in nine critically ill patients treated by continuous venovenous hemofiltration (CVVH). All patients received one dose of 1 g of meropenem intravenously. High-flux polysulfone membranes were used as dialyzers. Meropenem levels were measured in plasma and ultrafiltrate by high-performance liquid chromatography. The total body clearance and elimination half-life were 143.7 +/- 18.6 ml/min and 2.46 +/- 0.41 h, respectively. The post- to prehemofiltration ratio of meropenem was 0.24 +/- 0.06. Peak plasma drug concentrations measured 60 min postinfusion were 28.1 +/- 2.7 microgram/ml, and trough levels after 6 h of CVVH were 6.6 +/- 1.5 microgram/ml. The calculated total daily meropenem requirement in these patients with acute renal failure and undergoing CVVH was 2,482 +/- 321 mg. Based on these data, we conclude that patients with severe infections who are undergoing CVVH can be treated effectively with 1 g of meropenem every 8 h.