To evaluate the influence of obesity on pharmacokinetics of amiodarone (AMD) using Non-Linear Mixed Effects Modelling (NONMEM) in Japanese patients treated with oral therapy.Method:
Serum concentrations of AMD were determined by high performance liquid chromatography. One hundred and fifty-one trough concentrations from 23 patients receiving repetitive oral AMD were collected. Body mass index (BMI) and body fat percentage were measured.Results:
Estimates generated using NONMEM indicated that the clearance of AMD was influenced by BMI, age and daily dosage of AMD. The final pharmacokinetic model wasCL(L/h) = 0·16 · TBW · 0·53AGE ≥ 65 · 0·78BMI ≥ 25 · DD0·51,Vd (L) = 10·2 · TBW, whereCLis total body clearance, TBW is total body weight (kg), DD (mg/kg/day) is daily dosage of AMD, AGE (years) ≥65 = 1 for patient was 65 years old or over and 0 otherwise, BMI (kg/m2) ≥25 = 1 for patient was 25 kg/m2 or over and 0 otherwise andVd is apparent volume of distribution. The clearance of AMD decreased significantly by 22·3% with a BMI higher than 25 kg/m2. The clearance of AMD also decreased significantly by 46·9% when patient age was more than 65 years.Conclusion:
Population pharmacokinetic analysis confirms that obesity affects the pharmacokinetics of AMD.