Interspecies pharmacokinetic scaling of DA-8159, a new erectogenic, in mice, rats, rabbits and dogs, and prediction of human pharmacokinetics.
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.
Shim
Hyun J
HJ
College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Republic of Korea.
Kim
Yu C
YC
Lee
Joo H
JH
Kwon
Jong W
JW
Kim
Won B
WB
Kim
Yoon G
YG
Kim
So H
SH
Lee
Myung G
MG
D000284:Administration, Oral; D000818:Animals; D019540:Area Under Curve; D001835:Body Weight; D002851:Chromatography, High Pressure Liquid; D004285:Dogs; D006207:Half-Life; D006801:Humans; D007275:Injections, Intravenous; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D011743:Pyrimidines / Q000008:administration & dosage / Q000493:pharmacokinetics*; D011817:Rabbits; D051381:Rats; D013045:Species Specificity; D013449:Sulfonamides; D000096926:Benzenesulfonamides
D011743:Pyrimidines; D013449:Sulfonamides; C419664:udenafil; D000096926:Benzenesulfonamides