Computer dosing program for the initiation of vancomycin therapy.
The predictive performance of a computer dosing program used for initiating vancomycin therapy was studied. Initial serum vancomycin concentrations in 31 adult patients receiving vancomycin were estimated by using a computer program (T.D.M.S.) incorporating a two-compartment open model. Sixty-two serum vancomycin concentrations at steady state (Css) were obtained before and after one-hour infusions and compared with estimated Css values. Bias and precision were evaluated by calculating median error (ME) and median absolute error (MAE), respectively. Population-based estimates of volume of distribution (V) and clearance (CL) were compared with those obtained by fitting each patient's data set by using Bayesian analysis (BA) and non-linear least-squares regression (NLLS). Median (mean +/- S.D.) bias and precision for peak Css were 7.7 (10.2 +/- 10.8) and 7.7 (10.6 +/- 10.5) mg/L, and for trough Css were 7.4 (7.7 +/- 7.6) and 7.4 (8.8 +/- 6.2) mg/L. The medians were significantly different from zero. Estimated median (mean +/- S.D.) V, CL, and half-life were 0.72 L/kg, 0.60 (0.67 +/- 0.21) mL/min/kg, and 11.59 (12.87 +/- 3.91) hours. Median (mean +/- S.D.) CL values determined by BA and NLLS were 0.86 (0.89 +/- 0.32) and 0.85 (0.92 +/- 0.34) mL/min/kg, respectively. Both CL values were significantly greater than the population-based estimate. However, median V values determined by BA and NLLS did not differ from the population-based estimate. A revised clearance model derived from Bayesian analysis of data for the first 21 patients was tested in the 10 other patients and appeared to improve the predictive performance of the a priori model.(ABSTRACT TRUNCATED AT 250 WORDS)
Ito
M K
MK
University of the Pacific (UOP) School of Pharmacy, Stockton, CA.
Duren
L L
LL
Simonian
J S
JS
Dreyfus-Vigil
S D
SD
Cookson
T L
TL
D000328:Adult; D015982:Bias; D003198:Computer Simulation; D003404:Creatinine / Q000378:metabolism; D004360:Drug Therapy, Computer-Assisted; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D008657:Metabolic Clearance Rate; D015203:Reproducibility of Results; D014640:Vancomycin / Q000008:administration & dosage / Q000097:blood* / Q000493:pharmacokinetics / Q000627:therapeutic use*
D014640:Vancomycin; D003404:Creatinine