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Continuing our BCS topic, this week we will look at Class 4 drugs:
Low Permeability, Low Solubility
Class 4 drugs exhibit poor and variable bioavailability attributed to slow dissolution rate, poor permeability, and slow gastric emptying. Limited or even no in vitro-in vivo correlation is expected. These drugs are not suitable for controlled-release preparations.
List of Class 4 Drugs
Examples include:
| Acetaminophen | Colistin | Mebendazole |
| Acetazolamide | Ciprofloxacin | Methotrexate |
| Amphotericin B | Cyclosporin A | Neomycin |
| Bifonazole | Doxycycline | Paclitaxel |
| Cephalexin | Ellagic acid | Ritonavir |
| Chlorothiazide | Furosemide | Saquinavir |
| Chlorthalidone | Hydrochlorothiazole | Tobramycin |
| Cefuroxime | Linezolid | |
Because of the low permeability and low solubility of these drugs, both uptake and efflux transporters play an important role in their oral bioavailability. Most Class 4 drugs are substrate for P-glycoprotein (low permeability) and substrate for CYP 3A4 (extensive pre-systemic metabolism), which further potentiates the problem of poor therapeutic potential. Years ago, Class 4 drugs were the exception rather than the rule; however, today, many new drugs in the pipeline are in this category.
Involved in formulating this class of drugs can be:
- Enhancing their solubility
- Use of permeation enhancers
Methods to enhance both solubility and permeability were discussed in the previous two newsletters.
Loyd V. Allen, Jr., PhD, RPh
Editor-in-Chief
International Journal of Pharmaceutical Compounding
Remington: The Science and Practice of Pharmacy Twenty-second edition
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