Influence of food and body weight on the pharmacokinetics of penticainide

Summary— The pharmacokinetics of penticainide, a class Ic antiarrhythmic drug, was studied in 16 healthy adults (eight males and eight females) after a single 300-mg oral dose in fasting conditions and with a standard meal. Penticainide concentrations in plasma and urine were measured by hplc. The pharmacokinetic parameters of penticainide including C_max, t_max, AUC and t_1/2 were not significantly altered in the presence of food. AUC values (mean ± sd) were 50.68 ± 10.8 mg·h·l⁻¹ and 49.52 ± 9.87 mg·h·l⁻¹ in the absence and presence of food, respectively. However, a significant difference was observed between males and females in both fasting and fed conditions with a higher value of the apparent oral clearance in the second group. The values of apparent oral clearance, expressed in weight-normalized units were 1.33 ± 0.35 ml·mn⁻¹·kg⁻¹ (male) and 1.93 ± 0.34 ml·mn⁻¹·kg⁻¹ (female) in fast conditions ( P < 0.01) and 1.38 ± 0.28 ml·mn⁻¹·kg⁻¹ (male) and 1.93 ± 0.49 ml·mn⁻¹·kg⁻¹ (female) in fed conditions ( P < 0.02), respectively. The pharmacokinetics of penticainide is not modified by the presence of food, but an influence of body weight may be considered.