Gentamicin pharmacokinetics in an elderly population

Rick Tharp, BSP, RPh
Presented at the 27th Annual ASHP Midyear Clinical Meeting

Gentamicin is an economical antibiotic which has retained excellent gram-negative activity during 25 years of wide-spread clinical use. However, despite this extensive use, published data on the pharmacokinetics of gentamicin in the elderly is limited.

Objective

The objective of this study was to describe the pharmacokinetic parameters of gentamicin in an acutely ill elderly population.

Methods

All elderly patients on the general medical/surgical floor who were prescribed gentamicin were included in the study. Seventy years of age or older was chosen as the definition of elderly.

Pharmacists calculated gentamicin dosages and scheduled serum sampling times for all study patients. Initial dosages were calculated using the Hull and Sarrubi method.1

Creatinine clearance was estimated with the method of Cockroft and Gault with adjustment to body surface area.2 Patients with a diagnosis of liver disease were excluded from the study because of possible interference with creatinine clearance determinations.

Gentamicin was administered by a 60 minute intermittent intravenous infusion. Gentamicin serum measurements were obtained after the patient's pharmacokinetic variables were assumed to have reached steady-state (four times the estimated half-life). The trough level was obtained 15 to 30 minutes before administration of the sample dose. The peak level was obtained 15 to 30 minutes after the sample dose had infused. The exact infusion times a sampling times were recorded for all patients. The serum concentration time data for individual patients were fitted to a one-compartment model by the linear regression method described by Sawchuk and Zaske.3

Results

Forty-four patients were studied, five were excluded from the study because of inaccurate recording of sampling or non-compliance with the prescribed regimen. Patient demographics are presented in Table 1.

Table 1. Patient demographics
Age (years) 81.8 +/- 6.8 (70-95)
Gender (M/F) 18/21
Weight (kg) 61.6 +/- 16.7 (33.2-109.1)
Creatinine Clearance
(ml/min/1.73 m2)
37.9 +/- 10.9
(14-66)

The results of the pharmacokinetic determinations are presented in Table 2. Large interpatient variability in pharmacokinetic parameters were observed.

Table 2. Pharmacokinetic parameters
Elimination rate
(L/hr)
0.133 +/- 0.046
(0.066-0.23)
Half-life
(hours)
5.92 +/- 2.17
(3.01-10.5)
Volume of distribution
(L/kg)
0.29 +/- 0.06
(0.18-0.48)
Clearance
(ml/min)
37.9 +/- 14.5
(14.5-71.5)

The gentamicin apparent volume of distribution ranged from 0.18 to 0.48 L/kg with a mean of 0.29 L/kg, see Figure 1. This is significantly greater than the 0.25 L/kg average Vd cited in the literature.4 Seventy-four percent of the study population had a volume of distribution greater than 0.25 L/kg.

Volume of distribution

The mean elimination half-life in the elderly study group was 5.92 +/- 2.17 hours. This is substantially longer than the average 2 hour half-life of gentamicin reported in the literature.4 As would be expected for a drug which is eliminated chiefly by the kidneys, there was a significant correlation between gentamicin clearance and creatinine clearance. (Pearson's correlation coefficient = 0.687, p<0.0001), see Figure 2.

Clearance

Conclusion

An acutely ill elderly population had a slightly larger gentamicin volume of distribution than that reported in the literature. This elderly population also exhibited a substantially longer gentamicin half-life. There was a significant correlation between gentamicin clearance and creatinine clearance in this population.

References

  1. Sarubbi FA, Hull JW. Gentamicin serum concentrations: pharmacokinetic predictions. Ann Intern Med 1976;85:183-189.
  2. Cockroft DW, Gault MH. Prediction of creatinine clearance from serum creatinine. Nephron 1976; 16: 31-33.
  3. Sawchuck RJ, Zaske DE, et al. Kinetic model for gentamicin dosing. Clin Pharmacol Ther 1977;21;3:262-269.
  4. Conte JE, Barre SL. Manual for antibiotics and infectious disease, 6th ed. Philadelphia. Lea & Febiger, 1988; p 52.

Click here to return to previous page