PURPOSE: To predict the absolute oral bioavailabilities (BAs) of drugs in humans without using pharmacokinetic data from intravenous administration in humans. METHODS: The distribution volume of the terminal phase (Vd(beta)) in humans was predicted by three methods using animal pharmacokinetic data. Then, total body clearance (CL(tot)) was calculated by multiplying the elimination rate constant and Vd(beta), and the BA was calculated as a ratio between CL(tot) and oral clearance. The predicted and observed values were compared for 67 drugs for which pharmacokinetic data after intravenous administration in humans were available. RESULTS: For Vd(beta), predicted values within twice the observed value were obtained for 72.1% of drugs by both methods Ia and Ib, respectively, in which only rat pharmacokinetic data were used. The corresponding percentage was 75.0% for method II, in which pharmacokinetic data from animals other than rats were used. For BA, predicted values within 1.3 times the observed values were obtained for 66.7% and 57.4% of drugs by methods Ia and Ib, respectively, and 75.0% by method II. CONCLUSIONS: Using the present methods, it is possible to predict BA from human oral administration data combined with animal pharmacokinetic data to a certain level without using intravenous injection data.
PURPOSE: To predict the absolute oral bioavailabilities (BAs) of drugs in humans without using pharmacokinetic data from intravenous administration in humans. METHODS: The distribution volume of the terminal phase (Vd(beta)) in humans was predicted by three methods using animal pharmacokinetic data. Then, total body clearance (CL(tot)) was calculated by multiplying the elimination rate constant and Vd(beta), and the BA was calculated as a ratio between CL(tot) and oral clearance. The predicted and observed values were compared for 67 drugs for which pharmacokinetic data after intravenous administration in humans were available. RESULTS: For Vd(beta), predicted values within twice the observed value were obtained for 72.1% of drugs by both methods Ia and Ib, respectively, in which only rat pharmacokinetic data were used. The corresponding percentage was 75.0% for method II, in which pharmacokinetic data from animals other than rats were used. For BA, predicted values within 1.3 times the observed values were obtained for 66.7% and 57.4% of drugs by methods Ia and Ib, respectively, and 75.0% by method II. CONCLUSIONS: Using the present methods, it is possible to predict BA from human oral administration data combined with animal pharmacokinetic data to a certain level without using intravenous injection data.
Authors: T Izumi; S Enomoto; K Hosiyama; K Sasahara; A Shibukawa; T Nakagawa; Y Sugiyama Journal: J Pharmacol Exp Ther Date: 1996-06 Impact factor: 4.030