Carbamazepine and the active epoxide metabolite are effectively cleared by hemodialysis followed by continuous venovenous hemodialysis in an acute overdose

Hemodialysis (HD) and continuous venovenous hemodialysis (CVVHD) have an unproven role in the management of carbamazepine overdose. Albumin‐enhanced CVVHD may accelerate carbamazepine (CBZ) clearance, but no pharmacokinetic data has been reported for traditional CVVHD without albumin enhancement. In addition, it is unclear whether the active CBZ‐epoxide metabolite is removed with either mode of dialysis. We present a case of CBZ intoxication successfully managed with sequential HD and CVVHD. The CBZ half‐life during CVVHD was 14.7 hours, compared with the patient's endogenous half‐life of 30.8 hours. The CBZ‐epoxide half‐life was 3.2 hours during HD. We conclude that HD and CVVHD provide effective clearance of CBZ and the epoxide metabolite and should be considered in the management of an acute toxic ingestion.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/86953/1/j.1542-4758.2011.00563.x.pd

Pharmacokinetics of ertapenem in critically ill patients receiving continuous venovenous hemodialysis or hemodiafiltration

This study characterizes the pharmacokinetics of ertapenem, a carbapenem antibiotic, in critically ill adult subjects receiving continuous renal replacement therapy (CRRT). Eight critically ill patients with suspected/known Gram-negative infections receiving continuous venovenous hemodialysis (CVVHD) or continuous venovenous hemodiafiltration (CVVHDF) and ertapenem were enrolled. One gram of ertapenem was infused over 30 min. Predialyzer blood samples were drawn with the first dose of ertapenem from the hemodialysis tubing at time zero, 30 min, and 1, 2, 4, 8, 12, 18, and 24 h after the start of the ertapenem infusion. Effluent was collected at the same time points. Ertapenem total serum, unbound serum, and effluent concentrations from all eight subjects were used simultaneously to perform a population compartmental pharmacokinetic modeling procedure using NONMEM. Monte Carlo simulations were performed to evaluate the ability of several ertapenem dosing regimens (500 mg once daily, 750 mg once daily, 500 mg twice daily, and 1,000 mg once daily) to obtain effective unbound serum concentrations above 0.5, 1, and 2 ?g/ml. For our simulated patients, all regimens produced unbound ertapenem concentrations above 2 ?g/ml for 40% of the dosing interval for at least 96% of simulated patients. (This study has been registered at ClinicalTrials.gov under registration no. NCT00877370.)Merck & Co. provided funding for this investigator-initiated study.Scopu