Interspecies pharmacokinetic scaling of DA-8159, a new erectogenic, in mice, rats, rabbits and dogs, and prediction of human pharmacokinetics

Abstract

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.

Tuberculous Granulomas Are Hypoxic in Guinea Pigs, Rabbits, and Nonhuman Primates

“…The doses were chosen to attempt to simulate the expected human exposure to these two agents on the basis of the fact that 10 mg/kg Rif gives a maximal concentration in serum of 10 g/ml in mice (18), approximately the same as the maximal concentration in the sera of humans after ingestion of a single 600-mg dose (29). Interspecies allometric scaling of exposure generally correlates with the weight of the animal; thus, the exposure of rabbits should be lower than that of mice but still slightly higher than that of humans (38). After a single 500-mg dose of oral Mtz in humans, maximal concentrations in serum are approximately 5 to 10 g/ml (16).…”

Pharmacokinetics of Liquiritigenin in Mice, Rats, Rabbits, and Dogs, and Animal Scale-Up

“…8 Therefore, we combined the pharmacokinetic parameters of LQ after its intravenous administration at a dose of 20 mg/kg to four animal species, that is, mice, rats, rabbits, and dogs, to investigate interspecies correlation and to predict human pharmacokinetics of the drug. Animal scale-up of the pharmacokinetic parameters of DA-8159 (udenafil; Zydena 1 ), 9 an inhibitor of phosphodiesterase 5 (PDE 5) for the treatment of male erectile dysfunction, and CS-023, 10 a parenteral carbapenem antibiotic, by allometric scaling, and prediction of the plasma concentration-time profiles in humans using complex Dedrick plot 11 have been published. The purpose of this paper is to report the pharmacokinetics of LQ after its intravenous and/or oral administration with various doses to mice, rats, rabbits, and dogs, and to investigate interspecies relationship of the pharmacokinetic parameters of LQ, such as the total body clearance (CL) and apparent volume of distribution at steady state (V ss ) to predict the pharmacokinetics of the drug in humans from the four animal data.…”

Effects of omeprazole or cola beverage on the pharmacokinetics of oral DA‐8159, a new erectogenic, in rats

“…Hence, the significantly greater AUC of DA-8159 with omeprazole could be due to inhibition of metabolism of DA-8159 by inhibition of CYP3A1/2 by omeprazole. As mentioned earlier, this could not be due to increased oral absorption of DA-8159 in rats with omeprazole since approximately 99% of the oral dose of DA-8159 was absorbed in rats [3].…”