Time-averaged total body clearance (Cl) and apparent volume of distribution at steady state (V(SS)) of DA-8159 after intravenous administration to mice (30 mg/kg), rats (30 mg/kg), rabbits (30 mg/kg) and dogs (3 mg/kg) were analysed as a function of species body weight (W) using the allometric equation for interspecies scaling, and were used to predict those in humans. Significant linear relationships were obtained between log Cl (l/h) and log W (kg) (r = 0.992; p = 0.0079) and log V(SS) (l) and log W (kg) (r = 0.999; p < 0.0001). The corresponding allometric equations were Cl = 4.36 W(0.492) and V(SS) = 6.41 W(0.911). These allometric equations were extrapolated to predict the Cl and V(SS) for DA-8159 in humans based on the 70 kg body weights. In addition, concentrations in the plasma-time profile predicted using the four animal data fitted to a complex Dedrick plot of animal data. Our results indicated that the DA-8159 data obtained from four laboratory animals could be utilized to generate preliminary estimates of the pharmacokinetic parameters in humans. These parameters can serve as guidelines for better planning of clinical studies.

The total body clearance (Cl), renal clearance (Clr), and apparent volume of distribution at steady state (Vss) of DA‐1131, a new carbapenem, after intravenous (iv) administration of the drug, 50 mg kg−1, to mice, rats, rabbits, and dogs were analysed as a function of species body weight (W) using the allometric equation for interspecies scaling, and were used to predict these parameters in humans. Significant linear relationships were obtained between log[Cl (L h−1)] and log[W (kg)] (r = 0.995; p = 0.00503), log[Clr (L h−1)] and log[W (kg)] (r = 0.998; p = 0.0429), and log[Vss (L)] and log[W (kg)] (r = 0.987; p = 0.0126). The corresponding allometric equations were Cl = 0.706W0.811, Clr = 0.318W0.888, and Vss = 0.194W0.981. These allometric equations were extrapolated to predict the Cl and Vss for DA‐1131 in humans based on 70 kg body weight. The Cl and Vss for humans predicted from the four animal data well fitted to regression lines of animal data. Interspecies scale‐up of plasma concentration–time data for the four species using a complex Dedrick plot resulted in similar profiles. In addition, the concentration in plasma–time profile predicted using the four animal data well fitted to a complex Dedrick plot of animal data. Our results indicate that the DA‐1131 data obtained from laboratory animals could be utilized to generate preliminary estimates of the pharmacokinetic parameters in humans. These parameters can serve as guidelines for better planning of clinical studies. © 1998 John Wiley & Sons, Ltd.

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