Doripenem and meropenem pharmacokinetics differ in obesity. However, currently approved dosing regimens provide adequate pharmacodynamic exposures for susceptible bacteria in obese patients.

Monitoring free phenytoin concentration is clinically useful for patients with uremia, hepatic disease, hypoalbuminemia, and related conditions. Free phenytoin is commonly measured by immunoassay in the protein-free ultrafiltrate prepared by centrifuging serum for 20-30 minutes, using an appropriate ultrafiltration device. We studied the effect of centrifugation time (15-40 minutes) and protein concentrations on ultrafiltration volume, and the related effects on measured free phenytoin concentrations. Temperature was ambient for all studies. The ultrafiltration volumes were directly proportional to centrifugation time and were inversely proportional to the protein concentrations. Although ultrafiltration volume significantly increased with longer centrifugation time, the measured free phenytoin concentrations did not increase proportionately. The concentration of phenytoin in the residual serum retained in the ultrafiltration device did not change proportionally either. Therefore, equilibrium of phenytoin concentrations between the ultrafiltrate and retentate was maintained, regardless of centrifugation time or protein concentration.

This article describes a rapid isocratic high-performance liquid chromatographic (HPLC) method for the simultaneous measurement of the anticonvulsants levetiracetam and zonisamide. Monitoring these drugs is important for detecting potentially toxic concentrations, particularly in patients with renal impairment, but no commercial assays are currently available. Following a liquid-liquid extraction, levetiracetam (5-150 microg/mL) and zonisamide (5-80 microg/mL) are quantitated by HPLC-UV. The assay's limit of quantitation, linearity, imprecision, and accuracy adequately cover the therapeutic range of these drugs. The assay should be attractive to clinical laboratories because the run time for quantification of both drugs is approximately 5 min per sample, and no interferences are currently known.

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High-dose busulfan is an important component of many bone marrow transplantation-preparative regimens. High busulfan plasma levels have been shown to increase the chance of venoocclusive disease and low levels are associated with recurrence of disease or graft rejection. Currently, busulfan levels are monitored by physical methods that are expensive and time consuming, resulting in relatively low overall use of busulfan testing for dose adjustment. Novel highly selective antibodies for busulfan have been generated and a microtiter plate immunoassay capable of quantifying busulfan levels in plasma has been developed. The assay was configured using a busulfan-horseradish peroxidase (HRP) conjugate as the reporter group and busulfan monoclonal antibodies. The assay requires 30 microL of plasma with no sample preparation. The immunoassay has a standard curve based on busulfan with a range of 75-2000 ng/mL. The time to first result is 30 minutes with up to 40 patient samples in duplicate; multiple plates can be run at once. The coefficient of variation (CV) on signal is <5% for an entire plate, and the 95% confidence interval for negative samples (n = 78) is below the lowest calibrator of 75 ng/mL. Cross-reactivity with the major inactive metabolites (tetrahydrothiophene, tetramethyl sulfone, and tetrahydrothiophene-3-ol-1,1-dioxide) was <0.1%. Results generated with clinical samples (n = 35 and n = 70) correlate well to gas chromatography-mass spectrometry (R = 0.976 and 0.985, respectively) with a slope of 1.05 +/- 0.05. This immunoassay method is suitable for determining levels of busulfan in human plasma. It offers the advantages of using a smaller sample size, does not require sample preparation, and is less labor intensive than other methods. The ability to make 240 determinations per hour enables effective and timely routine monitoring of busulfan levels in clinical practice.