A meta-analysis was performed on the reported literature regarding followings. First, values of the Michaelis-Menten constants (K_m), maximal velocities (V_max), and intrinsic clearance (V_max/K_m) and the metabolic activities mediated by human cytochrome P450 3A4 and/or 3A5; second, inhibition constants (K_i); and third, maximum inactivation rate constants (k_inact) to establish the contribution of P450 3A5 to drug metabolism. At least 120 of the 127 metabolic reactions investigated (>94%) were catalyzed by P450 3A4 and by P450 3A5. In the 73 metabolic reactions for which data were available, the mean P450 3A5/P450 3A4 ratios of K_m, V_max, and V_max/K_m values were 1.93, 1.25, and 1.20, respectively, but the median ratios were 1.17, 0.64, and 0.56, respectively. In 14-18% of the metabolic reactions, the V_max and V_max/K_m values for P450 3A5 were more than twice those for P450 3A4. The K_i values for P450 3A5 were on average approximately 5 times those for P450 3A4. Five of 13 mechanism-based inhibitors of P450 3A4 (38%) did not exhibit similar mechanism-based inhibition of P450 3A5. These collective findings give insight into the contribution of polymorphic P450 3A5 to drug metabolism and adverse drug interactions.