No abstract

Busulfan is an alkylating agent used in preparative regimens before bone marrow transplantation (BMT). Busulfan concentrations in plasma, expressed as the area under the concentration-time curve (AUC), were reported to correlate with treatment outcome. Because busulfan is administered in 16 doses of 1 mg/kg every 6 hours for 4 days, the opportunities to "correct" the dose as a consequence of the measured AUC are limited to the 16-dosage protocol. In the present research busulfan pharmacokinetics were prospectively evaluated in 27 adult patients treated according to the above protocol by measuring the first, second, and fifth dose AUC. The pharmacokinetic analysis was based on a noncompartment model for extravascular absorption, but calculations according to a 1-compartment model gave similar results. A simple mathematical approximation allowed prediction of the AUC of the second dose from that of the first and the busulfan concentration at trough. Fifteen patients had the dose adjusted at the fourth dose to obtain an AUC within the "therapeutic window" of 950-1500 microM-min. This procedure was then validated by the measurement of the fifth dose AUC. It appears that this simple pocket calculator method allows a rapid evaluation of the need and the extent of dose adjustment and proved to be a valuable tool to improve busulfan administration in pre BMT treatment.

Introduction One session of water-pipe tobacco smoking (WPS) can increase carboxyhemoglobin (COHb) to levels comparable to those reported in carbon monoxide poisoning, which may cause memory impairment and confusion. Methods A prospective study evaluating healthy volunteers pre- and post-30 min of WPS session. Primary outcome parameters were executive cognitive measures [digit span test and Paced Auditory Serial Addition Test (PASAT)]. The effect of repeated cognitive testing 30 min apart without WPS was evaluated in age- and sex-matched healthy volunteers. Secondary outcome parameters included cardio-pulmonary, COHb, serum nicotine, and cytokine changes. Results Thirty-five subjects aged 25.6 ± 4.5 years smoked water-pipe for a 30-min session. Control group included 20 subjects aged 25.2 ± 5.1 years. Digit span test median score decreased after WPS (16 and 15, respectively, p = .003), insignificant decrease in controls. Median PASAT score increased after WPS (49 and 52, respectively, p = .009); however, a much larger significant increase was observed in controls (p ≤ .001). One WPS session resulted in significant increases in heart and respiratory rates and significant decrease in FEF25–75%. Post WPS, median COHb levels increased (from 2.2% to 10.7%, p < .0001) as did median serum nicotine levels (from 1.2 to 26.8 ng/mL, p < .0001). Serum cytokines levels: IL-2 and IL-6 increased (p < .0001 for each), and IL-10 and IL-5 decreased (p < .0001 and p = .04, respectively). Conclusions One session of WPS resulted in significant negative effects on cognitive executive measures, significant increases in COHb and serum nicotine levels, and significant changes in serum cytokines. Our findings call for increasing awareness towards the possible consequences of cognitive alterations following a 30-min session of WPS. Implications One 30-min session of water-pipe smoking resulted in negative effects on executive cognitive measures, increased carboxyhemoglobin and serum nicotine, and significant changes in serum cytokine levels. This study adds to the accumulating evidence on the harmful effects of water-pipe smoking, a growing epidemic, and calls for awareness of its possible consequences of acute cognitive alterations.

The everolimus QMS immunoassay, using the Architect ci4100 analyzer, had a significant positive bias compared with LC-MS/MS, with a wide range between the limits of agreement. The lack of agreement may result in inadequate everolimus dose adjustments, suggesting that the QMS assay cannot be used interchangeably with the LC-MS/MS method for therapeutic everolimus monitoring in organ-transplanted patients.