Allometrically scaled data sets (138 compounds) used for predicting human clearance were obtained from the literature. Our analyses of these data have led to four observations. (1) The current data do not provide strong evidence that systemic clearance (CL(s); n = 102) is more predictable than appar
Prediction of human drug clearance from two species: A comparison of several allometric methods
β Scribed by Kosalaram Goteti; C. Edwin Garner; Iftekhar Mahmood
- Publisher
- John Wiley and Sons
- Year
- 2010
- Tongue
- English
- Weight
- 147 KB
- Volume
- 99
- Category
- Article
- ISSN
- 0022-3549
No coin nor oath required. For personal study only.
β¦ Synopsis
The objective of the study was to assess the degree of accuracy in human drug clearance prediction from two species using four different allometric approaches: simple allometry (SA), multiexponential allometry (ME), rule of exponents (ROE), and fixed exponents (FE) as suggested by Tang et al. There were 45 compounds in this analysis and the two species used were either rat-dog or rat-monkey. In addition, > or = 3 species scaling was also performed to evaluate the comparative accuracy in the prediction of human drug clearance between two or more than two-species scaling. The results of the study indicated that the two-species scaling with different methods provided different degrees of accuracy in the prediction of clearance. Prediction by a particular method was also species dependent. For example, a given drug with rat-dog scaling provided a reasonably accurate prediction of clearance whereas with rat-monkey scaling the prediction of clearance was highly erratic or vice versa. The results of the study indicated that the two-species scaling can be useful for prediction purposes but the prediction of clearance from > or = 3 species was far more accurate than two-species scaling.
π SIMILAR VOLUMES
Pharmacokinetic (PK) interspecies scaling is generally conducted using PK data from at least three animal species but three animal species may not be always available. In a recent manuscript, Tang et al. have described the methods to predict human drug clearance using one or two animal species. The
This study was conducted to comprehensively evaluate the performance of various allometric scaling methods for the prediction of human clearance. Allometric scaling was used to predict clearance for 103 compounds, for which clearance data in the rat, dog, monkey, and humans were available. Allometry
The objective of this study is to evaluate the predictive performance of the rule of exponents (ROE) and 'fu Corrected Intercept Method' (FCIM) for the human drug clearance. Different classes of drugs such as extensively metabolized, renally excreted, renally secreted, and biliary excreted drugs wer
In Table 3, the MAE value for three-species allometric scaling using the rule of exponents should be 6.44, not 11.03 as originally cited. This error resulted from an incorrect predicted value for one of the 103 compounds in the dataset (nicotine; incorrect error of 479.6 mL/min/kg rather than the co