Evaluation of the pharmacokinetics of linezolid in an obese Japanese patient.

We evaluated the pharmacokinetics of linezolid in the case of an obese Japanese patient (body weight 116 kg; body mass index 37 kg/m(2)). Linezolid was administered at a dose of 600 mg by intravenous drip infusion for 60-90 min at 12-h intervals. The results showed increased clearance of linezolid and a reduced serum concentration compared to population pharmacokinetic parameters, with trough levels below the 90% minimum inhibitory concentration. However, linezolid was effective for improving lung infection and inflammation in our patient, which may be due to its particularly effective transfer into lung tissues. Linezolid undergoes slow non-enzymatic oxidation in vivo that may be increased in obese patients, and this may account for the greater clearance. Our findings are useful for the planning of linezolid therapy in obese patients.

Pharmacokinetics and protein binding of linezolid in cerebrospinal fluid and serum in a case of post-neurosurgical bacterial meningitis.

We describe a case of bacterial meningitis in a patient administered linezolid (LZD). The ratio of free to total LZD concentrations in cerebrospinal fluid (CSF) was 1 for all measurements, and the LZD concentration in CSF measured at the trough level was almost the same as the free serum concentration.

Thrombocytopenia and anemia caused by a persistent high linezolid concentration in patients with renal dysfunction.

It has been proposed that it is not necessary to adjust the dose of linezolid (LZD) in patients with reduced renal function. However, significantly lower platelet counts and hemoglobin levels have been reported in such patients compared to those in patients with normal renal function. This suggests that the appropriate dose and administration method for LZD are yet to be established in patients with renal dysfunction. The subjects in this study were patients with renal dysfunction who developed adverse effects of thrombocytopenia and anemia during treatment with LZD. We investigated the association of these adverse effects with the blood LZD concentration and the area under the concentration-time curve from zero to 24 h (AUC(0-24)), determined using a one-compartment Bayesian model (n = 20). The measured blood LZD concentration was significantly higher than the predicted concentration in a population pharmacokinetics approach (p < 0.01), and severe thrombocytopenia developed as the blood LZD concentration increased. The platelet count and hemoglobin level decreased as the AUC(0-24) of LZD increased in patients with renal dysfunction, and the correlations were significant: r = 0.593 and r = 0.783, respectively (p < 0.01). These findings suggest that LZD administered to patients with renal dysfunction may reach a high blood level and subsequently increase the AUC(0-24), which may then induce adverse effects of severe thrombocytopenia and anemia.

[Correlation of pharmacokinetic parameters with serum vancomycin concentration in elderly patients with malignancies].

Vancomycin (VCM) is a glycopeptide antibiotic that is generally used to treat methicillin-resistant Staphylococcus aureus (MRSA). Recently, it has been reported that VCM clearance (CL) is significantly higher in elderly patients and infants and children with malignancies, compared with those without malignancies. We have treated many patients with a variety of malignant tumors in whom serum VCM concentrations were found to be moderately lower during therapeutic drug monitoring (TDM). The aim of this study was to determine whether the presence of malignant tumors influences trough concentrations of VCM and VCM pharmacokinetics in elderly patients during treatment for MRSA infection. Comparison of the clinical characteristics and VCM pharmacokinetic parameters between patients with and without malignancies was undertaken in 49 elderly Japanese patients infected with MRSA. The mean trough concentration of VCM in patients with malignancies was significantly lower than that in patients without malignancies. Our results showed significantly higher values of VCM CL and volume of distribution and a shorter elimination half-life in patients with malignancies. Univariate logistic regression analysis of the pharmacokinetic parameters indicated that VCM CL contributed as a significant factor independent of the relation to malignant tumor. In conclusion, it is suggested that the therapeutic effects and side effects of VCM should be actively monitored using TDM, because concentrations may decrease when CL increases in VCM therapy for elderly patients with malignant tumors.