Updated US and European Dose Recommendations for Intravenous XXXX : How Do They Perform?

@entity1 @entity3273 @entity1011
BACKGROUND:    The US Food and Drug Administration (FDA) and European Medicines Agency (EMA) have approved updated dose recommendations for intravenous @entity3273 in @entity1 with various degrees of renal function. We assessed the recommendations in relation to their ability to achieve clinically relevant plasma @entity3273 concentrations. METHODS:    Pharmacokinetic data from 162 adult critically ill @entity1 ( @entity1011 clearance range, 5.4-211 mL/min) were used to determine the average steady-state plasma @entity3273 concentration (Css,avg) that would be achieved if each @entity1 received the FDA or EMA dose. Target attainment rates for FDA- and EMA-approved daily doses to achieve @entity3273 Css,avg of >= 0.5, >= 1, >= 2, and >= 4 mg/L were determined for each @entity1011 clearance category (>= 80 mL/min, 50 to <80 mL/min, 30 to <50 mL/min, and <30 mL/min). RESULTS:    For @entity1011 clearance <30 mL/min, 100% of @entity1 receiving the EMA dose achieved a @entity3273 Css,avg >= 1 mg/L, but the attainment rate was as low as 53.1% for @entity1 receiving the FDA-approved dose. For @entity3273 Css,avg >= 2 mg/L, the attainment rates were 87.5% with the EMA dose but only 6.3%-34.4% in @entity1 receiving the FDA dose. Differences in attainment rates for a @entity3273 Css,avg of >= 2 mg/L and >= 4 mg/L extended to @entity1 with @entity1011 clearance 30 to <50 mL/min. For @entity1 with @entity1011 clearance >= 80 mL/min, only approximately 65%-75% of @entity1 achieved a @entity3273 Css,avg of >= 1 mg/L with either set of recommendations. CONCLUSIONS:    The study highlights important differences between the FDA- and EMA-approved dose recommendations and informs the setting of clinical breakpoints. CLINICAL TRIALS REGISTRATION:    NCT00235690.
