About the Drug Permeability Calculator
The Drug Permeability Calculator is a scientifically validated, web-based ADME (Absorption, Distribution, Metabolism, Excretion) screening tool that predicts intestinal drug absorption and membrane permeability using established in vitro models including Caco-2 cell monolayers and Parallel Artificial Membrane Permeability Assay (PAMPA). By integrating key physicochemical descriptors—logP, polar surface area (PSA), molecular weight (MW), hydrogen bond donors/acceptors, and rotatable bonds—this Drug Permeability Calculator provides quantitative estimates of passive transcellular diffusion, the primary route for oral drug absorption.
Built on peer-reviewed QSAR models and the Lipinski Rule of Five, this tool enables rapid assessment of drug-likeness and permeability risk in early-stage drug discovery, significantly reducing late-stage attrition due to poor pharmacokinetics.
Scientific Models and Methodology
The calculator implements three complementary permeability prediction models:
1. Caco-2 Permeability Model
Caco-2 cells derived from human colorectal carcinoma form polarized monolayers that mimic intestinal epithelium. Apparent permeability (Papp) is measured in cm/s:
Interpretation:
- Papp > 10 × 10⁻⁶ cm/s: High permeability (well-absorbed)
- 1–10 × 10⁻⁶ cm/s: Moderate
- < 1 × 10⁻⁶ cm/s: Low permeability
2. PAMPA Model
Artificial lipid membranes predict passive diffusion without active transport:
3. Lipinski Rule of Five
Empirical guidelines for oral bioavailability:
- MW ≤ 500 Da
- logP ≤ 5
- H-bond donors ≤ 5
- H-bond acceptors ≤ 10
Importance of Drug Permeability Assessment
Poor permeability is responsible for ~40% of drug development failures. Early prediction enables:
- Hit-to-lead optimization with permeability-aware design
- Reduced animal testing through in silico screening
- Cost savings by eliminating poor candidates early
- Improved success rates in clinical trials
When and Why You Should Use This Calculator
Use the Drug Permeability Calculator during:
- Virtual screening of compound libraries
- Lead optimization in medicinal chemistry
- ADME profiling of natural products
- Academic research on drug delivery
- Formulation development for oral drugs
Ideal Applications:
- Pharmaceutical R&D laboratories
- Contract research organizations (CROs)
- University drug discovery programs
- Regulatory submission support
User Guidelines for Accurate Results
To ensure reliability:
- Use computed or measured values from reliable sources (ChemAxon, ACD/Labs)
- Input neutral form properties (not ionized)
- Validate with known drugs:
- Aspirin: MW=180, logP=1.2, PSA=63 → High permeability
- Propranolol: MW=259, logP=3.0, PSA=41 → Reference compound
- Consider pH effects for ionizable groups
Purpose and Clinical Relevance
This calculator serves to:
- Quantify passive diffusion potential
- Identify permeability liabilities
- Guide structural modifications
- Support regulatory dossiers
Interpretation of Results
The calculator provides:
- Caco-2 Papp: Human intestinal absorption prediction
- PAMPA: Passive diffusion component
- Absorption %: Estimated fraction absorbed
- Lipinski score: 0–4 violations
Limitations and Considerations
Model limitations include:
- Passive diffusion only (no active transport)
- Limited to small molecules
- Does not predict metabolism or efflux
- Requires experimental validation for critical decisions
References and Further Reading
- Lipinski CA, et al. (1997). Experimental and computational approaches to estimate solubility and permeability. Adv Drug Deliv Rev.
- Veber DF, et al. (2002). Molecular properties that influence oral bioavailability. J Med Chem.
- Hou T, et al. (2007). ADME evaluation in drug discovery. J Chem Inf Model.
- Artursson P, et al. (1991). Caco-2 monolayers in experimental drug absorption. Biochem Biophys Res Commun.
- Kansy M, et al. (1998). Physicochemical high throughput screening: PAMPA. J Med Chem.
For agricultural applications of bioactive compounds, visit Agri Care Hub. Learn more about membrane transport on the Drug Permeability Calculator Wikipedia page.