Interspecies pharmacokinetic scaling of DA-8159, a new erectogenic, in mice, rats, rabbits and dogs, and prediction of human pharmacokinetics
| Autor: | Yoon Gyoon Kim, Yu C. Kim, Hyun J. Shim, Myung Gull Lee, Won B. Kim, Jong W. Kwon, Joo H. Lee, So H. Kim |
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| Rok vydání: | 2005 |
| Předmět: |
Male
Veterinary medicine Administration Oral Pharmaceutical Science Body weight Mice Animal data Dogs Species Specificity Pharmacokinetics Interspecies scaling Animals Humans Pharmacology (medical) Chromatography High Pressure Liquid Pharmacology Volume of distribution Mice Inbred ICR Sulfonamides Chemistry Body Weight Total body General Medicine Rats Predictive factor Pyrimidines Area Under Curve Injections Intravenous Rabbits Steady state (chemistry) Half-Life |
| Zdroj: | Biopharmaceutics & Drug Disposition. 26:269-277 |
| ISSN: | 1099-081X 0142-2782 |
| DOI: | 10.1002/bdd.455 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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