Abstract
To validate the population pharmacokinetic parameters of aminoglycoside disposition in patients with cancer, a retrospective evaluation of predictive performance of a Bayesian program was performed in 155 patients from 1986 to 1989 who received amikacin, gentamicin or tobramycin. Each patient received 1 of the 3 drugs and had initial drug concentration determination, with a second set of drug concentrations drawn ⩽14 days after the initial dose. Predictions of 64 amikacin, 144 gentamicin and 102 tobramycin concentrations were generated using 1-compartment model pharmacokinetic parameters, serum creatinine values, patients’ dosage history and demographic data. The mean (± SD) observed (and predicted) serum concentrations for amikacin were 18.9 ± 14.8 mg/L (17.2 ± 14.1 mg/L); for gentamicin were 4.49 ± 3.58 mg/L (4.26 ± 3.33 mg/L) and for tobramycin were 4.52 ± 3.70 mg/L (4.05 ± 3.49 mg/L) [p > 0.05]. Results demonstrated minimal bias with a mean error in gentamicin concentrations of −0.236 (95% CI −0.533: 0.0613). Significant (p <0.05) underprediction occurred in concentrations of tobramycin [−0.474 mg/L (95% CI −0.842: −0.0107)] and amikacin [−1.77 mg/L (95% CI −3.42: −0.114)]. Good precision is indicated by a mean squared error for gentamicin of 3.35 mg/L (95% CI 1.70: 4.99) and for tobramycin of 3.64 mg/L (95% CI 1.83: 5.44). Fair precision is demonstrated by amikacin [46.1 mg/L (95% CI 27.3: 65.0)]. Similar results were shown in a separate peak/trough analysis. These data indicate that aminoglycoside pharmacokinetics in patients with cancer can be predicted with minimal bias and good precision using a Bayesian forecasting program for gentamicin and tobramycin.
| Original language | English |
|---|---|
| Pages (from-to) | 79-87 |
| Number of pages | 9 |
| Journal | Clinical Pharmacokinetics |
| Volume | 24 |
| Issue number | 1 |
| DOIs | |
| State | Published - 1993 |
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All Science Journal Classification (ASJC) codes
- Pharmacology (medical)
- Pharmacology
- Pharmacology, Toxicology and Pharmaceutics(all)
Cite this
Aminoglycoside Forecasting in Neutropenic Patients with Cancer. / Kosirog, Jane L.; Rospond, Raylene M.; Destache, Christopher J.; Hall, Phillip.
In: Clinical Pharmacokinetics, Vol. 24, No. 1, 1993, p. 79-87.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Aminoglycoside Forecasting in Neutropenic Patients with Cancer
AU - Kosirog, Jane L.
AU - Rospond, Raylene M.
AU - Destache, Christopher J.
AU - Hall, Phillip
PY - 1993
Y1 - 1993
N2 - To validate the population pharmacokinetic parameters of aminoglycoside disposition in patients with cancer, a retrospective evaluation of predictive performance of a Bayesian program was performed in 155 patients from 1986 to 1989 who received amikacin, gentamicin or tobramycin. Each patient received 1 of the 3 drugs and had initial drug concentration determination, with a second set of drug concentrations drawn ⩽14 days after the initial dose. Predictions of 64 amikacin, 144 gentamicin and 102 tobramycin concentrations were generated using 1-compartment model pharmacokinetic parameters, serum creatinine values, patients’ dosage history and demographic data. The mean (± SD) observed (and predicted) serum concentrations for amikacin were 18.9 ± 14.8 mg/L (17.2 ± 14.1 mg/L); for gentamicin were 4.49 ± 3.58 mg/L (4.26 ± 3.33 mg/L) and for tobramycin were 4.52 ± 3.70 mg/L (4.05 ± 3.49 mg/L) [p > 0.05]. Results demonstrated minimal bias with a mean error in gentamicin concentrations of −0.236 (95% CI −0.533: 0.0613). Significant (p <0.05) underprediction occurred in concentrations of tobramycin [−0.474 mg/L (95% CI −0.842: −0.0107)] and amikacin [−1.77 mg/L (95% CI −3.42: −0.114)]. Good precision is indicated by a mean squared error for gentamicin of 3.35 mg/L (95% CI 1.70: 4.99) and for tobramycin of 3.64 mg/L (95% CI 1.83: 5.44). Fair precision is demonstrated by amikacin [46.1 mg/L (95% CI 27.3: 65.0)]. Similar results were shown in a separate peak/trough analysis. These data indicate that aminoglycoside pharmacokinetics in patients with cancer can be predicted with minimal bias and good precision using a Bayesian forecasting program for gentamicin and tobramycin.
AB - To validate the population pharmacokinetic parameters of aminoglycoside disposition in patients with cancer, a retrospective evaluation of predictive performance of a Bayesian program was performed in 155 patients from 1986 to 1989 who received amikacin, gentamicin or tobramycin. Each patient received 1 of the 3 drugs and had initial drug concentration determination, with a second set of drug concentrations drawn ⩽14 days after the initial dose. Predictions of 64 amikacin, 144 gentamicin and 102 tobramycin concentrations were generated using 1-compartment model pharmacokinetic parameters, serum creatinine values, patients’ dosage history and demographic data. The mean (± SD) observed (and predicted) serum concentrations for amikacin were 18.9 ± 14.8 mg/L (17.2 ± 14.1 mg/L); for gentamicin were 4.49 ± 3.58 mg/L (4.26 ± 3.33 mg/L) and for tobramycin were 4.52 ± 3.70 mg/L (4.05 ± 3.49 mg/L) [p > 0.05]. Results demonstrated minimal bias with a mean error in gentamicin concentrations of −0.236 (95% CI −0.533: 0.0613). Significant (p <0.05) underprediction occurred in concentrations of tobramycin [−0.474 mg/L (95% CI −0.842: −0.0107)] and amikacin [−1.77 mg/L (95% CI −3.42: −0.114)]. Good precision is indicated by a mean squared error for gentamicin of 3.35 mg/L (95% CI 1.70: 4.99) and for tobramycin of 3.64 mg/L (95% CI 1.83: 5.44). Fair precision is demonstrated by amikacin [46.1 mg/L (95% CI 27.3: 65.0)]. Similar results were shown in a separate peak/trough analysis. These data indicate that aminoglycoside pharmacokinetics in patients with cancer can be predicted with minimal bias and good precision using a Bayesian forecasting program for gentamicin and tobramycin.
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U2 - 10.2165/00003088-199324010-00007
DO - 10.2165/00003088-199324010-00007
M3 - Article
C2 - 8448975
AN - SCOPUS:0027400260
VL - 24
SP - 79
EP - 87
JO - Clinical Pharmacokinetics
JF - Clinical Pharmacokinetics
SN - 0312-5963
IS - 1
ER -