In patients with renal insufficiency, dose adjustments based on creatinine clearance and body weight have been a component of imipenem dosage instructions. The objective of the current analysis was to provide revised dosing recommendations by evaluating the impact of creatinine clearance and body weight on the pharmacokinetics of imipenem. A population pharmacokinetics model was developed with data from 465 patients and 3300 pharmacokinetic samples. Simulations provided data to support revision of the dosing recommendations to remove body weight-adjusted dosing, and the analysis formed the basis for updates that are reflected on the current imipenem label for both the United States and Europe. The optimized regimen provided an advantage in terms of improved target attainment at breakpoint minimum inhibitory concentration values of 1 and 2 μg/mL, as low-body-weight patients maintained >90% probability of target attainment compared to <90% probability of target attainment achieved with the previously approved regimen. It was concluded that additional dose adjustments for body weight were not necessary and the new scheme would simplify dosing while maintaining patient safety and efficacy.
Keywords: antibiotics; dose; imipenem; infectious disease; pharmacokinetic; pharmacometrics; population pharmacokinetics.
© 2018, The American College of Clinical Pharmacology.