Science is a cruel mistress [RSABE / ABEL]
Hi Anand,
A manifold of reasons:
:
❝ Why drug having highly variable […] any specific reason?
A manifold of reasons:
- Drugs in BCS Class IV (low permeability & solubility) generally show high variability (both within and between subjects). See also the BDDCS (introduced by Wu and Benet)1,2.
- The high variability may as well be not a property of he drug itself, but of the formulation*. Delayed release products are infamous for that. Here it is mainly the physiologic variability in gastric transit which hurts (where monolithic formulations ≥ multiparticular ones).
- High first-pass effect or presystemic metabolization in the gut wall. Enzymes might also get saturated at higher doses. In such a case variability increases with dose.
- Excipients may influence transporters in the gut wall, gastric motility, in vivo solubilty / stability.
- And, and, and…
library(PowerTOST)
CV <- 0.4
# FDA
sampleN.RSABE(CV=CV, theta0=0.9, design="2x2x4", details=F)
sampleN.RSABE(CV=CVp2CV(CV=CV, ratio=0.67), theta0=0.9, design="2x2x4", details=F)
# EMA
sampleN.scABEL(CV=CV, theta0=0.9, design="2x2x4", details=F)
sampleN.scABEL(CV=CVp2CV(CV=CV, ratio=0.67), theta0=0.9, design="2x2x4", details=F)
- Wu C-Y, Benet LZ. Predicting drug disposition via application of BCS: transport/absorption/elimination interplay and development of a biopharmaceutics drug disposition classification system. Pharm Res. 2005;22(1):11–23. doi:10.1007/s11095-004-9004-4.
- Benet LZ, Broccatelli F, Oprea TI. BDDCS Applied to Over 900 Drugs. AAPS J. 2011;13(4):519–47. doi:10.1208/s12248-011-9290-9.
free resource
- Hence, the distinction between HVDs (Highly Variable Drugs) and HVDPs (Highly Variable Drug Products). The former show high variability already if administered as a solution.
—
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Helmut Schütz
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Dif-tor heh smusma 🖖🏼 Довге життя Україна!
![[image]](https://static.bebac.at/pics/Blue_and_yellow_ribbon_UA.png)
Helmut Schütz
![[image]](https://static.bebac.at/img/CC by.png)
The quality of responses received is directly proportional to the quality of the question asked. 🚮
Science Quotes
Complete thread:
- Drug Variability ISCV Anand 2015-07-28 13:47 [RSABE / ABEL]
- Science is a cruel mistressHelmut 2015-07-28 14:31