PKP-010 Levetiracetam clinical pharmacokinetics in elderly patients with epilepsy

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Abstract

Background

Levetiracetam (LEV) is increasingly used in the elderly due to a favourable pharmacokinetic profile, good tolerability and no significant drug–drug interactions. LEV is renally excreted, and its clearance is expected to decrease during old age because of the physiological reduction in glomerular filtration rate.

Purpose

To compare apparent steady state oral clearance of levetiracetam (LEV CL/F) in elderly versus non-elderly patients with epilepsy.

Material and methods

This was a retrospective study from 2009 to 2013 in 380 adult patients with epilepsy treated with LEV. Inclusion criteria: age ≥16 years; treatment with LEV for at least 1 month; and venous blood sampling before the first morning dose of LEV. Variables collected were dose, serum concentration, age, sex, body weight and anticonvulsant comedications prescribed. They were obtained from the therapeutic drug monitoring register and the medical records. Patients were grouped according to age: group A (16–30 years, n=93), group B (31–50 years, n=131), group C (51–65 years, n=90) and group D (>65 years, n=66). In group D, 15.15% of patients had impaired renal function (creatinine clearance <50 mL/min). Serum concentrations of LEV were measured by high performance liquid chromatography with spectrophotometric detection. Stata version 12 software was used for statistical analysis.

Results

Mean basal LEV serum concentrations (µg/mL) significantly increased with age. We compared group A (13.32±4.54) versus B (14.01±6.43) (NS); group A vs C (17.54±5.45) (p<0.0001) and group A vs D (20.21±8.34) (p<0.0001). Hence we compared younger patients (groups A and B; 13.66±5.48) versus group C (p<0.0001) and group D (p<0.0001). Mean weight normalised LEV CL/F (mL/min/kg) progressively decreased with age. We compared group A (1.45±0.76) versus B (1.41±0.85) (NS); group A versus C (1.18±0.83) (p<0.0001) and group A versus D (0.95±0.68) (p<0.0001). We also compared group A versus D without patients with impaired renal function (0.98±0.58) (p<0.0001). Finally, we compared non-elderly patients (groups A and B; 1.43±0.81) versus group C (p<0.0001) and group D (p<0.0001).

Conclusion

LEV CL/F significantly declined with ageing, with a reduction in median values ranging from 20% in patients aged 50–65 years to 35% in those over 65 years compared with non-elderly patients. To achieve a given serum drug concentration, LEV dose should be reduced by around 30% in elderly patients compared with younger subjects.

Conclusion

No conflict of interest

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