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Biomedical subjects

Ian Wilding

Publications and source records attributed to Ian Wilding.

5 recordsLinked to original sources
PubMed2007

Systemic availability of the active metabolite hydroxy-fasudil after administration of fasudil to different sites of the human gastrointestinal tract.

This study evaluated the gastrointestinal absorption of fasudil, a novel Rho kinase inhibitor for the treatment of stable angina, at different sites using remote-controlled capsules and assessed the feasibility of developing an extended-release formulation. Ten healthy male volunteers were enrolled, and 8 subjects completed this single-dose, open-label, randomized, 5-way crossover study. Forty milligrams of fasudil HCl was administered as solution to the distal ileum and ascending colon, as powder to the ascending colon, and orally as an immediate-release tablet and solution. All treatments were well-tolerated and no serious adverse events were observed. The mean systemic availabilities of M3 relative to the oral solution were 1.04 (distal ileum, solution), 1.14 (ascending colon, solution), 1.27 (ascending colon, powder) and 1.04 (oral tablet), indicating similar systemic availability of M3 after administration of fasudil HCl to different gastrointestinal sites. The results suggest that development of a once-a-day extended-release formulation for fasudil HCl should be readily achievable.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
PubMed2003

Pharmacokinetics and delivery of the anti-influenza prodrug oseltamivir to the small intestine and colon using site-specific delivery capsules.

This study investigated the site-specific absorption of oseltamivir using targeted delivery and gamma scintigraphy. On four separate occasions, nine healthy male subjects each received a single 150 mg of oseltamivir administered via the Enterion capsule to the stomach, proximal small bowel, distal small bowel and the ascending colon. Pharmacokinetic parameters of oseltamivir and its carboxylate metabolite show that absorption was similar in the proximal and distal small bowel compared to stomach delivery, but reduced from the ascending colon, demonstrating that absorption-rate limited disposition occurred only for the ascending colon. The metabolite-to-parent ratios were minimally reduced. The results support the feasibility of modified-release formulation development whilst confirming the high and consistent oral bioavailability of oseltamivir.

Acetamides↗
PubMed2003

Pharmacoscintigraphic assessment of the regional drug absorption of the dual angiotensin-converting enzyme/neutral endopeptidase inhibitor, M100240, in healthy volunteers.

M100240 is the thioester of MDL 100,173, a dual angiotensin-converting enzyme (ACE)/neutral endopeptidase (NEP) inhibitor currently in phase II development. The purpose of this study was to evaluate the relative bioavaibility of M100240 in various regions of the gastrointestinal tract using the Enterion capsule, a noninvasive radiocontrolled device providing targeted drug delivery, to explore the absorption characteristics of M100240 in healthy volunteers. In addition, the absolute bioavailability of an immediate-release formulation of M100240 was assessed. Pharmacokinetic data were obtained from 13 healthy subjects in an open-label, single-dose, randomized, five-period crossover study. Treatments included 25 mg M100240 administered via short intravenous infusion, oral immediate-release tablet administration, and oral Enterion capsule delivery of drug substance to the proximal small bowel, distal small bowel, and ascending colon. Each treatment was separated by a 14-day drug-free washout period. The localization of the Enterion capsule in the gastrointestinal tract was monitored using scintigraphic imaging. M100240 and MDL 100,173 plasma concentrations were quantified using a validated LC/MS/MS method, and pharmacokinetic parameters were calculated using noncompartmental methods. The estimates of relative bioavailability in the proximal small bowel, distal small bowel, and ascending colon relative to the oral immediate-release tablet are approximately 94%, 97%, and 41%, respectively. M100240 is primarily absorbed throughout the proximal and distal small bowel with modest absorption in the ascending colon. The absolute bioavailability estimate of the M100240 immediate-release formulation is 49%. These data characterize the fundamental in vivo performance attributes of M100240, thereby providing an approach for optimizing prototype modified-release formulations for this compound.

Adult↗
PubMed2002

Bioequivalence testing for locally acting gastrointestinal products: what role for gamma scintigraphy?

Bioequivalence testing for locally acting gastrointestinal products is a challenging issue for both the pharmaceutical industry and the global regulatory authorities. It is widely accepted that for medicinal products not intended to be delivered into the systemic circulation, pharmacokinetic bioavailability cannot be used. However, it is becoming increasingly accepted that local availability may be assessed, where appropriate, by approaches that qualitatively reflect the presence of the active substance at the site of action. These methods must be specifically chosen for that combination of active substance and route of drug delivery. This paper argues for the use of gamma scintigraphy as a validated measure of local availability and bioequivalence for topically acting products administered to the gastrointestinal tract by the oral and rectal route.

Administration, Oral↗