Christopher J H Porter

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Highly potent, but poorly water-soluble, drug candidates are common outcomes of contemporary drug discovery programmes and present a number of challenges to drug development - most notably, the issue of reduced systemic exposure after oral administration. However, it is increasingly apparent that formulations containing natural and/or synthetic lipids(More)
In recent years there has been an increase in interest in the utility of lipid based delivery systems, at least in part as a result of the effective development of lipid based products such as Sandimmun Neoral (cyclosporin), Norvir (ritonavir) and Fortovase (saquinavir). The development pathway for lipid based formulations, however, is still largely(More)
Degradation of human growth hormone (hGH) at the injection site has previously been implicated as the basis for its reduced systemic availability following subcutaneous (SC) administration. The goal of these studies was to develop an animal model which would allow mass balance calculations to (i) quantify the loss at the injection site and (ii) determine(More)
Oral lipid-based drug delivery systems may include a broad range of oils, surfactants, and cosolvents. This diversity makes comparison of lipid-based formulations difficult. Although the relationship between formulation and drug absorption is understood at a conceptual level, performance in vivo cannot be predicted with confidence at present. The Lipid(More)
Postprandial administration of halofantrine (Hf), an important antimalarial, leads to 3- and 12-fold increases in oral bioavailability in humans and beagles, respectively, and corresponding 2.4-fold and 6.8-fold decreases in metabolic conversion to desbutylhalofantrine (Hfm). Factors contributing to the decreased postprandial metabolism of Hf could include(More)
P-glycoprotein (P-gp)-mediated drug efflux from the apical membrane of enterocytes is believed to modulate intestinal cytochrome P450 3A (CYP3A) metabolism by altering substrate access to the CYP3A enzyme. This interplay between P-gp and CYP3A was investigated in a rat in situ model of intestinal permeation, where a recirculating luminal perfusion of the(More)
Subcutaneous (s.c.) administration continues to be the main route for the delivery of protein drugs due to their poor bioavailability by most non-parenteral routes. While small drug molecules are rapidly and extensively absorbed after s.c. injection, the systemic bioavailability of protein drugs is often incomplete and variable. Given the widespread use of(More)
Intestinal fatty acid-binding protein (I-FABP) is a small protein that binds long-chain dietary fatty acids in the cytosol of the columnar absorptive epithelial cells (enterocytes) of the intestine. The binding cavity of I-FABP is much larger than is necessary to bind a fatty acid molecule, which suggests that the protein may be able to bind other(More)
Drugs are absorbed after oral administration as a consequence of a complex array of interactions between the drug, its formulation, and the gastrointestinal (GI) tract. The presence of food within the GI tract impacts significantly on transit profiles, pH, and its solubilization capacity. Consequently, food would be expected to affect the absorption of(More)
After oral administration, the majority of drug molecules are absorbed across the small intestine and enter the systemic circulation via the portal vein and the liver. For some highly lipophilic drugs (typically log P>5, lipid solubility>50 mg/g), however, association with lymph lipoproteins in the enterocyte leads to transport to the systemic circulation(More)