This small study suggests that a once-daily dosing regimen of tobramycin is at least as effective as and is no more and possibly less toxic than the twice-daily regimen. Using a single-dose therapy, peak concentration determination is not necessary, only trough samples should be monitored to ensure levels below 2 microg/ml.
Background: Pharmacokinetic parameters (PHK) of low-dose weekly paclitaxel (PAC) are not well known, particularly when administered with the cytoprotective agent amifostine (AMI). Methods: Patients with non-small cell lung cancer (NSCLC) received PAC alone or PAC + AMI. Blood samples were drawn at the end of the infusion at 0, 0.25, 0.5, 1, 2 and 4 h for the measurement of plasma PAC using HPLC. Area under the concentration-time curve (AUC), the peak plasma concentrations (Cmax) and the residence time of paclitaxel in plasma at concentrations >0.1 µM (TPP ≧0.1) and >0.05 µM (TPP ≧0.05) were calculated using a two-compartmental model. ANOVA was used for statistical analysis. Results: Pharmacokinetic studies were completed for 43 doses among 11 patients receiving PAC alone and for 26 doses among 8 patients receiving the combination AMI + PAC (from the first to the fifth week). Statistically significant differences in all parameters except AUC were observed between the 2 treatment groups. A significantly higher Cmax was observed for patients receiving PAC + AMI versus PAC alone. Both TPP ≧0.1 and TPP ≧0.05 were also more prolonged in AMI + PAC cycles. Conclusion: AMI produces a prolongation in PAC plasma circulation time. Further specifically designed studies are needed to quantify the resultant effects on PAC’s efficacy and toxicity.
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