Aminoglycoside pharmacokinetics in African-Americans with normal renal function.
OBJECTIVE
To compare aminoglycoside pharmacokinetics in African-Americans with normal renal function with published adult population values.


METHODS
An Institutional Review Board approved concurrent study.


METHODS
The study was conducted at Howard University Hospital, Washington DC.


METHODS
All subjects had serum creatinine levels of 1.5mg/dl or less and were receiving aminoglycoside for suspected or documented Gram-negative infection, had no obvious underlying disease condition that could influence aminoglycoside pharmacokinetics and were aged 18 years or older.


METHODS
Volume of distribution (Vd), half-life (t1/2), elimination rate constant (Ke) and total body clearance (Cl) were calculated using a one-compartment, open, linear pharmacokinetic model. Using an unpaired Student's t-test, the pharmacokinetic values of our patients were compared with general population values.


METHODS
Patients receiving aminoglycosides were identified by the pharmacist through the hospital's standard antibiotic order sheet. Twenty-five patients were enrolled after they met the inclusion criteria. Pharmacists made recommendations for dose change as part of standard of care when inappropriate doses were ordered. In collaboration with medical and nursing staff, the amount and time of dose administration, and steady-state peak and trough serum drug levels were stringently measured, documented on a data collection form and used to calculate pharmacokinetic values for our patients. The form was also used to document demographic information.


RESULTS
The following values were obtained: Vd 0.27+/-0.15 litres/kg, t(1/2) 1.93+/-1.38h, Ke 0.31+/-0.134/h (gentamicin), Ke 0.22 +/- 0.10/h (tobramycin), Cl 103.95+/-62.98ml/kg/h (gentamicin) and Cl 118.96+/-84.83ml/kg/h (tobramycin). These values are not significantly different from general population values. Following a mean tobramycin or gentamicin dose of 1.32+/-0.32mg/kg ideal body weight (IBW)/ dose or 1.11+/-0.33 mg/kg actual body weight (ABW)/ dose every 8h, patients achieved a mean peak and trough serum drug levels of 6.6+/-3.86mg/litre and 1.03+/-0.68mg/litre, respectively. Wide interpatient pharmacokinetic variability was also observed.


CONCLUSIONS
We conclude that aminoglycoside pharmacokinetics in African-Americans seem to be consistent with the published general population values. Thus, initiating aminoglycoside regimens using population dosing guidelines appears to be appropriate. However, due to the observed wide interpatient pharmacokinetic variability, individualized dosing is required with very close monitoring, to avoid or minimize toxicity.
Oparaoji
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EC
College of Pharmacy, Nursing and Allied Health, Howard University, Washington, DC 20059, USA.
Siram
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Elemihe
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Mezghebe
H M
HM
Cho
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Bashiri
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Piedrahita
K
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Pipalla
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RS
D000328:Adult; D000368:Aged; D000617:Aminoglycosides; D000900:Anti-Bacterial Agents / Q000009:adverse effects / Q000493:pharmacokinetics*; D044383:Black People; D003404:Creatinine / Q000097:blood; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D001741:Black or African American
D000617:Aminoglycosides; D000900:Anti-Bacterial Agents; D003404:Creatinine