Oral transmucosal delivery of eletriptan for neurological diseases.

Migraine is a highly prevalent neurological disease affecting circa 1 billion patients worldwide with severe incapacitating symptoms, which significantly diminishes the quality of life. As self-medication practice, oral administration of triptans is the most common option, despite its relatively slow therapeutic onset and low drug bioavailability. To overcome these issues, here we present, to the best of our knowledge, the first study on the possibility of oral transmucosal delivery of one of the safest triptans, namely eletriptan hydrobromide (EB). Based on a comprehensive set of in vitro and ex vivo experiments, we highlight the conditions required for oral transmucosal delivery, potentially giving rise to similar, or even higher, drug plasma concentrations expected from conventional oral administration. With histology and tissue integrity studies, we conclude that EB neither induces morphological changes nor impairs the integrity of the mucosal barrier following 4 h of exposure. On a cellular level, EB is internalized in human oral keratinocytes within the first 5 min without inducing toxicity at the relevant concentrations for transmucosal delivery. Considering that the pKa of EB falls within the physiologically range, we systematically investigated the effect of pH on both solubility and transmucosal permeation. When the pH is increased from 6.8 to 10.4, the drug solubility decreases drastically from 14.7 to 0.07 mg/mL. At pH 6.8, EB gave rise to the highest drug flux and total permeated amount across mucosa, while at pH 10.4 EB shows greater permeability coefficient and thus higher ratio of permeated drug versus applied drug. Permeation experiments with model membranes confirmed the pH dependent permeation profile of EB. The distribution of EB in different cellular compartments of keratinocytes is pH dependent. In brief, high drug ionization leads to higher association with the cell membrane, suggesting ionic interactions between EB and the phospholipid head groups. Moreover, we show that the chemical permeation enhancer DMSO can be used to enhance the drug permeation significantly (i.e., 12 to 36-fold increase). Taken together, this study presents important findings on transmucosal delivery of eletriptan via the oral cavity and paves the way for clinical investigations for a fast and safe migraine treatment.

Psychotropic drug versus psychotropic drug-update.

Psychotropic drugs are not necessarily the drugs of psychiatry. Seventy percent of antidepressants, and 90% of anxiolytics are prescribed by nonpsychiatric physicians. Since psychotropic medications are so frequently employed by nonpsychiatric physicians, e.g., neurologists, primary care physicians, internists, and because large numbers of their patients are concurrently on medical drugs for somatic reasons, the interactions of psychotropic versus medical drugs and psychotropic versus psychotropic drugs as listed below must be understood before primary care physicians or psychiatrists prescribe psychotropic medications, especially to the medically ill. Seventy commonly prescribed psychotropic drugs were examined for their interactions with other psychotropic medications using six reference tools: 1) MEDLINE (PubMed) employing the first generic psychotropic drug name, the second generic psychotropic drug name, and the term "interaction;" 2) Hanston's Drug Interaction Analysis and Management Text (quarterly updated version); 3) Drug Interactions Facts (Facts and Comparisons) (July 2001 quarterly updated version); 4) Micromedex Drug-dex; 5) American Hospital Formulary Service Drug Information; and 6) Food and Drug Administration (MedWatch) (Dear Doctor Letters and new labeling) ( for (1999, 2000, and 2001). The authors recognized that all of the above sources do not necessarily cover the entire information database regarding drug-drug interactions. (Citations regarding children, reports in foreign languages or concerning food, animals, in vitro experiments, analgesics, and naturalistic-herbal or natural products-treatment interactions were excluded).