PurposeBariatric surgery is nowadays commonly applied as treatment for morbid obesity (BMI > 40 kg/m2). As information about the effects of this procedure on a drug’s pharmacokinetics is limited, we aimed to evaluate the pharmacokinetics of CYP3A probe substrate midazolam after oral and intravenous administration in a cohort of morbidly obese patients that was studied before and 1 year post bariatric surgery.MethodsTwenty morbidly obese patients (aged 26–58 years) undergoing bariatric surgery participated in the study of which 18 patients returned 1 year after surgery. At both occasions, patients received 7.5 mg oral and 5 mg intravenous midazolam separated by 160 ± 48 min. Per patient and occasion, a mean of 22 blood samples were collected. Midazolam concentrations were analyzed using population pharmacokinetic modeling.ResultsOne year after bariatric surgery, systemic clearance of midazolam was higher [0.65 (7%) versus 0.39 (11%) L/min, mean ± RSE (P < 0.01), respectively] and mean oral transit time (MTT) was faster [23 (20%) versus 51 (15%) minutes (P < 0.01)], while oral bioavailability was unchanged (0.54 (9%)). Central and peripheral volumes of distribution were overall lower (P < 0.05).ConclusionsIn this cohort study in morbidly obese patients, systemic clearance was 1.7 times higher 1 year after bariatric surgery, which may potentially result from an increase in hepatic CYP3A activity per unit of liver weight. Although MTT was found to be faster, oral bioavailability remained unchanged, which considering the increased systemic clearance implies an increase in the fraction escaping intestinal first pass metabolism.Electronic supplementary materialThe online version of this article (doi:10.1007/s11095-015-1752-9) contains supplementary material, which is available to authorized users.

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Younger age--and not bodyweight--was significantly associated with higher cefazolin clearance. However, as in all patients with bodyweights up to 260 kg, unbound plasma cefazolin concentrations remained above 1 mg L(-1) until 4 h after the intravenous administration of a 2-g dose. As such, re-dosing within 4 h or dosing with another antibiotic class should only be considered in the case of a higher MIC(90) of the local isolates.

The intervention programme successfully reduced the occurrence of unacceptable pain. Further improvement of pain management should focus on the prevention of pain.

In contrast to conventional on-pump coronary artery bypass grafting only mild increase of parameters of oxidative stress is reported during and after off-pump coronary artery bypass grafting. In an attempt to reduce the side effects of extra corporeal circulation the mini- extra corporeal circulation concept was introduced. In this study peroperative oxidative stress biomarkers were compared using three different techniques for CABG (conventional, mini and off-pump). It concerns a prospective randomized pilot study of 60 aged patients (70+ years) divided over 3 study groups. During the peroperative time points there was a significant increase in the mean concentration of uric acid for the CCABG group. On arrival at the intensive care unit the mean concentrations decreased significantly. During the per-operative period all groups showed significant increase in the concentration of malondialdehyde, however, this increase was the steepest for the CCABG group. On arrival at the intensive care unit the mean concentration decreased significantly for all groups. We found only mild organ ischemia/reperfusion injury and oxidative stress in the OPCAB group and the MCABG group with respect to the CCABG group.

tcMEP monitoring seems to be a useful adjunct of the protective techniques and may cause substantial adjustments in strategy, reducing the incidence of postoperative paraplegia.

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The preliminary results suggest that S-100 protein in CSF may be a marker of clinical value in evaluating the effects of measures to detect and reduce spinal cord ischemia.