TABLE P3.2 Properties of Lipoamide, Nosolatol, and Disolvprazole Lipoamide Nosol
ID: 191049 • Letter: T
Question
TABLE P3.2 Properties of Lipoamide, Nosolatol, and Disolvprazole Lipoamide Nosolatol Disolvprazole Acid or Base Molecular mass Highest dose strength log P log D6.o Solubility pH 1-7.5 Fraction of oral dose Base 396 Da 150 mg 3.2 3.0 High: 1.0 g/1000 mL 99.0% Acid 365 Da 250 mg 2.1 1.8 Low: 0.5 g/1000 mL 99.2% Base 221 Da 50 mg 0.2 -2.8 High: 5 g/1000 mL 3-5% recovered as Main enzyme involved CYP2c9 Substrate for intestinal None known Substrate for intestinal None known Bioavailability factor (F) 0.21 metabolites in humans in its metabolism uptake transporter efflux transporter CYP3A4 None known P-gp 0.7 None OATPIA2 None known 0.5Explanation / Answer
1) Most drug penetrate the gastrointestinal membrane by transcellular passive diffusion. Here lipoamide has high log P and log D value which indicate good permeability of drug. Another factor size because molecular mass less than 500 Da are predicted to have good permeability. Lipoamide has less than 500 Da size and high log P and D value means it penetrate intestinal membrane by passive diffusion. drug absorbed on intestinal membrane is rapidly carried away from absorption site and maintain concentration gradient across the cell membrane.
Nosolatol has lower permeability as compare to lipoamide because of lower log p and D value. Nosolatol penetrate intestinal membrane at moderate rate through passive diffusion.
Disolvprazol has negative log D and low log P value which indicate high hydrophilicity and low lipophilicity, cant penetrate the cell membrane. Although this drug has small size still this compound not able to penetrate intestine.
2) for lipoamide which is high permeability and high solubility drug, extent of absorption is also high means these drugs are well absorbed.
Nasolatol has high permeability but low solubility this drug has lower absorption rate than lipoamide because poor solubility limit the extent of absorption.
Disolvparazol has high solubility and low permeability. Low permeability limit both rate and extent of drug absorption. Bioavailability is variable
3) importance of dissolution and gastrointestinal permeability in controlling the rate and extent of drug absorption , the biopharmaceutical classification system has been developed (BCS) . In this system drug are placed in one of a group depending upon whether they posses high or low solubility and permeability.
Lipoamide is class 1 drug high solubility and high permeability
Nosolatol class 2 drug high permeability and low solubility
Disolvparazol class 3 drug low permeability and high solubility
4) biopharmaceutics drug disposition classification system classify compound into 4 classes based on their permeability and solubility. This system predict the effect of efflux and uptake transporter as well as post absorption systemic levels following oral and intravenous dosing.
Lipoamide in class 1 high permeability and high solubility transportar effect minimal, it allow high concentration to saturate in gut to saturate both uptake and efflux transporter. Efflux transporter has measurable effect on penetration of compound through blood brain barrier.
Class2 high permeability low solubility Nosolatol : efflux transporter, it will pass through gut membrabe and uptake transporter has no effect on absorption.
Above 2 classes eliminate by metabolism
Class 3 low permeability high solubility disolvparazol : uptake and efflux transporter, this class eliminate by unchanged drug. This drug sufficient in gut lumen due to their solubilitybut uptake tranaporter is necessary to overcome the effect of poor permeability of compound . Sufficient penetration achieved by uptake transporter.
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