ABSTRACT
The oral route of administration is still by far the most ubiquitous method of drug delivery. Development in this area still faces many challenges due to the complexity and inhomogeneity of the gastrointestinal environment. In particular, dosing unpredictably relative to motility phase means the gastrointestinal environment is a random variable within a defined range. Here, we present a mass balance analysis that captures this variation and highlights the effects of gastrointestinal motility, exploring what impacts it ultimately has on plasma levels and the relationship to bioequivalence for high solubility products with both high and low permeability (BCS I and III). Motility-dependent compartmental absorption and transit (MDCAT) mechanistic analysis is developed to describe the underlying fasted state cyclical motility and how the contents of the gastrointestinal tract are propelled.
Subject(s)
Diethylcarbamazine/blood , Fatty Acids, Monounsaturated/blood , Fluorouracil/blood , Gastric Emptying/drug effects , Gastrointestinal Motility/drug effects , Gastrointestinal Transit/drug effects , Indoles/blood , Intestinal Absorption/drug effects , Administration, Oral , Anticholesteremic Agents/administration & dosage , Anticholesteremic Agents/blood , Anticholesteremic Agents/pharmacokinetics , Computer Simulation , Diethylcarbamazine/administration & dosage , Diethylcarbamazine/pharmacokinetics , Fatty Acids, Monounsaturated/administration & dosage , Fatty Acids, Monounsaturated/pharmacokinetics , Fluorouracil/administration & dosage , Fluorouracil/pharmacokinetics , Fluvastatin , Humans , Immunosuppressive Agents/administration & dosage , Immunosuppressive Agents/blood , Immunosuppressive Agents/pharmacokinetics , Indoles/administration & dosage , Indoles/pharmacokinetics , Lipoxygenase Inhibitors/administration & dosage , Lipoxygenase Inhibitors/blood , Lipoxygenase Inhibitors/pharmacokinetics , Male , Models, Biological , Tissue DistributionABSTRACT
We demonstrate here that the RSID-saliva test can be used as a test for human salivary alpha-amylase on samples routinely examined in forensic casework. We show that the RSID-saliva test detects salivary alpha-amylase at lower concentrations than the Phadebas Quantitative test, that the RSID-saliva test does not cross-react with forensically important human fluids and that the RSID-saliva test can be successfully integrated into the whole swab semen extraction method.
