Anthropometric data and acetylsalicylic acid pharmacokinetics

The relationship between anthropometric data and pharmacokinetic characteristics of acetylsalicylic acid (ASA) after administration of a single oral dose of 500 mg ASA, an oral and intravenous dose of 500 mg D,L-lysine-mono-acetylsalicylate (Lys-ASA) and an oral dose of 1,000 mg Lys-ASA were evaluated. Individual data from an open, randomized crossover trial in 13 healthy volunteers (age 18-50 years, 6 female, 7 male, height 158-189 cm, weight 45-118 kg) were re-analyzed using a non-compartmental approach. The influence of body weight, height, body surface area and age on pharmacokinetic characteristics (Cmax, Tmax, AUClast, MRTlast, t 1/2, Cl, Vd) was assessed using the multiple regression method and pairwise multiple correlations were calculated. Multiple regression analysis showed significant multiple correlation coefficients of approximately 0.86 for Cmax (500 mg Lys-ASA i.v., 1,000 mg Lys-ASA per os and 500 mg ASA per os), Cl and AUClast (1,000 mg Lys-ASA per os). Standardized regression values (beta) reflected a major contribution for height, weight and body surface area, but age was not a relevant factor. Pairwise comparisons confirmed negative correlations between anthropometric characteristics and Cmax, AUClast and MRTlast and positive correlations between anthropometric data, Cl and Vd. In conclusion, apart from Tmax and t 1/2, all pharmacokinetic characteristics were influenced by body weight, height and body surface area. Whereas repeated administration of high doses in patients with low body weights may give rise to toxic effects, acute single dose administration would not lead to significant under-dosing in tall or stout patients.