1. Laboratory of Applied Pharmacokinetics, Department of Medicine, University of Southern California School of Medicine, Los Angeles, California, USA, 2. Department of Pharmacy, Hospital Geriatrique Antoine Charial, Francheville, France. 3. University of Southern California School of Pharmacy, 4. Department of Pharmacy, Croix-Rousse Hospital, Lyon, France. 5. Department of Clinical Pediatric Pharmacology, Debrousse Hospital, Lyon, France. 6. Department of Pharmacy, Edouard Herriot Hospital, Lyon, France.

The pharmacokinetics of Amikacin were studied in 56 febrile episodes for 45 patients with severe neutropenia while using the USC*Pack PC Clinical Programs for adaptive control of their dosage regimens [223 drug levels]. The purpose of this study are: i] to estimate the pharmacokinetic parameters in this neutropenic population [56 episodes, I], ii] to evaluate the effect of the dosage regimen: once-a-day [22 episodes, II] versus bid or tid [34 episodes, III]. Patients [mean age 53.3 +/- 17.9], 23 men and 22 women, received amikacin [17.7 +/- 3.6 mg/kg/d at day 1] in a 30 minutes infusion. The mean estimated creatinine clearance [CCr] was 76 +/- 22.5 ml/min/1.73 m2 at day 1. The method used for the population modeling was the Non Parametric EM algorithm [NPEM2] which computes the complete probability density function for a 1 or a 2 compartment model. The parametrizations studied are: Clearance/Volume [CL/VOL], Elimination rate constant/Volume [Kel/VOL] and KS/VS with Kel = KS * CCr + 0.00693, VS = VOL/Weight for a 1 compartment pharmacokinetic model. The main results concerned CL and VS with: CL[I] = 4.94 +/- 2.71, CL[II] = 4.74 +/- 2.65, CL[III] = 5.14 +/- 2.75 l/h and VS[I] = 0.31 +/- 0.11, VS[II] = 0.34 +/- 0.10, VS[III] = 0.30 +/- 0.11 l/kg. Volume of distribution VS is not so large as expected and a slight difference appears between II and III. The pharmacokinetic parameters obtained for this population of neutropenic patients will be used thereafter for the daily adaptive control of Amikacine therapy in our haematologic/oncologic patients. The variability observed remains important and requires an individualization of the dosage regimen for each patient.

Recording the times of dosage administration and serum sampling by trained personnel resulted in significantly greater adherence to the protocol of therapeutic drug monitoring and in significantly greater precision in the achievement of desired serum concentration goals of aminoglycoside therapy than when relatively untrained personnel recorded it as a comparatively unemphasized part of their job. This was true even when only data of peak and trough serum concentrations were used. This study demonstrates that thoughtful data collection by appropriately trained nursing, pharmacy, or other clinical personnel is an essential part of therapeutic drug monitoring and plays a significant role in the optimal individualization of drug dosage regimens for patient care.