PURPOSE To evaluate a canine intestinal accessport model to study colonic absorption of drugs. The antiepileptic drugs phenytoin and gabapentin were chosen to study absorption of a lipophilic and hydrophilic compound, respectively. METHODS Drug plasma level-time plots were generated subsequent to small intestinal and colonic drug administration of both drugs. The poorly water-soluble phenytoi...

The delivery of hydrophilic drugs to the brain is limited by the various barriers in the brain. In this respect, the blood-brain barrier (BBB) is the most important barrier because it functions as a physical and metabolic barrier represented by the endothelial cells of brain capillaries. In order to treat brain diseases, drugs must pass the BBB by targeting them to internalizing transport syste...

Biotransformation is the major clearance mechanism of therapeutic agents from the body. Biotransformation is known not only to facilitate the elimination of drugs by changing the molecular structure to more hydrophilic, but also lead to pharmacological inactivation of therapeutic compounds. However, in some cases, the biotransformation of drugs can lead to the generation of pharmacologically ac...

Allosteric (long-range) interactions can be surprisingly strong in proteins of biomedical interest. Here we use bioinformatic scaling to connect prior results on nonsteroidal anti-inflammatory drugs to promising new drugs that inhibit cancer cell metabolism. Many parallel features are apparent, which explain how even one amino acid mutation, remote from active sites, can alter medical results. ...

Homogeneous distribution of poorly water-soluble drugs in polyvinylpyrrolidone (PVP), a hydrophilic carrier, is definitely a suitable way to improve the bioavailability of such drugs. However, fundamental knowledge of drug polymer interaction and comprehensive study of the thermal, structural and solubility properties of such binary systems is the prerequisite for the development of useful drug...