Interspecies scaling of biliary excreted drugs
Mahmood, I; Sahajwalla, C
HERO ID
726220
Reference Type
Journal Article
Year
2002
Language
English
PMID
| HERO ID | 726220 |
|---|---|
| In Press | No |
| Year | 2002 |
| Title | Interspecies scaling of biliary excreted drugs |
| Authors | Mahmood, I; Sahajwalla, C |
| Journal | Journal of Pharmaceutical Sciences |
| Volume | 91 |
| Issue | 8 |
| Page Numbers | 1908-1914 |
| Abstract | The objective of this study is to predict clearance of drugs in humans from animals which are excreted in the bile. Clearance (CL) of eight drugs known to be excreted in the bile were randomly selected from the literature. Scaling of CL was performed using at least three animal species. Using simple allometry, CL x mean life-span potential (MLP) or CL x brain weight, CLs of studied drugs were predicted in humans. The choice of one of the methods depended on the 'rule of exponents' as described by Mahmood and Balian. A 'correction factor' was calculated by adjusting bile flow rate based on the species body weight (bile flow = mL/day/kg body weight) or liver weight (bile flow = mL/day/kg liver weight). Using the 'rule of exponents' and combining it with the 'correction factor', the CLs of biliary excreted drugs were predicted in humans. Predicted CLs in humans from animals using simple allometry were several times higher for all eight drugs (% error [range] = 46-1703). Using the 'rule of exponents' and combining it with a 'correction factor' as described in this report provided a substantial improvement (% error [range] = 5-91) in the prediction of CL for biliary excreted drugs. The results of this study indicate that the CL of a biliary excreted drug may be overpredicted in humans and by applying the 'correction factor' employed here, the predictability of drug CL in humans from animal data may be significantly improved. |
| Doi | 10.1002/jps.10174 |
| Pmid | 12115817 |
| Is Certified Translation | No |
| Dupe Override | No |
| Is Public | Yes |
| Language Text | English |
| Is Qa | No |