ABSTRACT
Tazobactam is a new derivative of penicillinic acid sulfone, which functions as an irreversible inhibitor of many beta-lactamases. The disposition of tazobactam M1 metabolite after intravenous (i.v.) infusion of 3 g of piperacillin/0.375 g of tazobactam was evaluated in 26 subjects with various degrees of renal impairment. Participants in the study were 18 subjects with creatinine clearances (ClCR) ranging from 7.4-41.8 mL/min, 4 subjects maintained on continuous ambulatory peritoneal dialysis (CAPD), and 4 subjects undergoing chronic hemodialysis (HD). The pharmacokinetic parameters of piperacillin and tazobactam were evaluated and were similar to previous reports. Tazobactam M1 metabolite maximum plasma concentration increased as renal function declined. The terminal elimination half-life and area under the plasma concentration-time curve of the tazobactam M1 metabolite increased as renal function declined. The mean rate of recovery of the tazobactam M1 metabolite in hemodialysate during a 3- to 4.2-hour HD session 1 hour after the i.v. infusion of piperacillin/tazobactam was 25.3%. However, when HD was performed at 36-48 hours after the i.v. infusion, 57.6% of the tazobactam dose was recovered as M1 metabolite, suggesting further conversion of tazobactam to M1 metabolite. Peritoneal dialysis removed 15.8% (n = 2) of the tazobactam dose as the M1 metabolite. Using a dose of 3 g of piperacillin/0.375 g of tazobactam, the predicted maximum steady-state plasma concentrations of the tazobactam M1 metabolite are 14.6 micrograms/mL, 34.8 micrograms/mL, and 48.8 micrograms/mL for subjects with ClCR 20-40 mL/min (every 6 hour dosing), ClCR < 20 mL/min (every 8 hour dosing), and on CAPD (every 12 hour dosing), respectively.
Subject(s)
Drug Therapy, Combination/administration & dosage , Penicillanic Acid/analogs & derivatives , Renal Insufficiency/metabolism , Adult , Aged , Female , Humans , Infusions, Intravenous , Male , Metabolic Clearance Rate , Middle Aged , Penicillanic Acid/administration & dosage , Penicillanic Acid/pharmacokinetics , Peritoneal Dialysis, Continuous Ambulatory , Piperacillin/administration & dosage , Piperacillin, Tazobactam Drug Combination , Renal Dialysis , Renal Insufficiency/therapy , TazobactamABSTRACT
A 28-yr-old man developed asthma shortly after being exposed to nickel sulfate (NiSO4) in a metal-plating factory. Recordings of peak expiratory flow rates at work and for an off-work period showed increased variations at work, with best values on weekends. Allergy prick skin tests elicited an immediate reaction with NiSO4 at a concentration of 10 mg/ml. Experimental inhalation challenges with NiSO4 at the same concentration of 10 mg/ml for 60 sec produced a bronchial obstruction typical of an early asthmatic response. A control asthmatic subject with a similar level of sensitivity to histamine failed to react after the same inhalation of NiSO4, which suggests a specific rather than irritant mechanism for the reaction. the patient had evidence of IgE antibody to a NiSO4-human serum albumin antigen. His serum selectively bound 63 Ni, and the test was selectively blocked by nonlabeled nickel sulfate. These results, evaluated together, suggest the development of occupational asthma caused by allergy to NiSO4 in this patient.
