Population pharmacokinetics and optimization of the dosing regimen of digoxin in adult patients

Toshiaki Komatsu, Mami Morita, Futaba Miyaji, Takayuki Inomata, Junya Ako, Koichiro Atsuda

This study aimed to evaluate the population pharmacokinetics of digoxin in Japanese patients and establish a dosage regimen based on the pharmacokinetic data. We analyzed 287 serum digoxin samples from 192 individuals by using the nonlinear mixed effects model. We used simulations to optimize the dosage regimen of digoxin to achieve a high likelihood of the target concentration (0.5-0.8 ng/mL). The total body clearance (CL/F ([L/h]) was calculated using the following formula: CL/F = (1.21 + 0.0532 × CLcr [(mL/min]) × (1 + 0.787 × AMD), where CLcr is the creatinine clearance and AMD is 0 in the case of concomitant administration of amiodarone and 1 otherwise. To achieve the target concentration (0.5-0.8 ng/mL), the dosage of digoxin was 0.0625 mg/day (CLcr < 35 mL/min and AMD = 0); 0.125 mg/day (CLcr, 35-65 mL/min and AMD = 0); 0.1875 mg/day (CLcr, 65-100 mL/min and AMD = 0); 0.0625 mg/every other day (CLcr < 30 mL/min and AMD = 1); and 0.0625 mg/day (CLcr, 30-85 mL/min and AMD = 1). Our findings suggest that population parameters are useful for evaluating digoxin pharmacokinetics.