ReviewsDiurnal Changes in the Pharmacokinetic Behavior of AmikacinBleyzac, Nathalie* ; Allard-Latour, Béatrice* ; Laffont, Alain*† ; Mouret, Jacques* ; Jelliffe, Roger‡; Maire, Pascal*†Author Information *ADCAPT, Hôpital A. Charial, Francheville, France; †Laboratory of Applied Pharmacokinetics, ‡Division of Geriatric Medicine, University of Southern California, School of Medicine, Los Angeles, CA, USA Received Februrary 2, 1999; accepted December 27, 1999. Address correspondence and reprint requests to Nathalie Bleyzac, Pharmacy department—Debrousse Hospital, 29 rue Sœur Bouvier, 69005 LYON, France. Therapeutic Drug Monitoring: June 2000 - Volume 22 - Issue 3 - p 307-312 Buy Abstract This retrospective study evaluated possible differences in the pharmacokinetic behavior of amikacin between the morning (am) and evening (pm). Of 634 patients receiving amikacin therapy, 17 received a dose every 12 hours (an IV infusion at 8:00 am and 8:00 pm) with amikacin serum levels obtained after both the am and pm infusions. Pharmacokinetic parameter values were estimated by the nonparametric EM algorithm (USC*PACK clinical software) for a one-compartment model. All patient data were analyzed in three ways. The parameter values were estimated by fitting the model first only to the serum levels drawn following the am dose; second, only to the data following the pm dose; and third, to all serum levels (am + pm). Parameter values found were (mean, median, SD respectively): am: Kel = 0.181114 h−1, 0.224460 h−1, 0.058820 h−1; Vol = 23.657507 L; 23.376231 L; 1.353253 L; Cl = 4.326720 L·h−1, 5.303726 L·h−1, 1.447731 L·h−1; pm: Kel = 0.110151 h−1; 0.121295 h−1; 0.016860 h−1; Vol = 28.948043 L; 24.091703 L; 9.266628 L; Cl = 3.081761 L·h−1, 2.810615 L·h−1; 0.705874 L·h−1; am + pm: Kel = 0.165321 h−1; 0.131796 h−1; 0.075425 h−1; Vol = 25.479043 L; 26.187970 L; 5.367054 L. These findings are in agreement with the known diurnal rhythm of glomerular filtration rate. Because pharmacokinetic parameter values are most often estimated using am data, this may lead to an overevaluation of these values compared with pm or to values for the entire day. The resulting drug regimens may therefore be overestimated regarding the elimination rate constant and underestimated regarding the volume of distribution. © 2000 Lippincott Williams & Wilkins, Inc.