Optimal Perfusion Rate Determined for In Situ Intestinal Absorption Studies in Rats

• Published in: Journal of pharmaceutical sciences 1981-03, Vol.70 (3), p.239-243
• Main Authors: Savina, Paul M., Staubusx, A.E., Gaginella, T.S., Smith, D.F.
• Format: Article
• Language: English
• Subjects: Absorption; Absorption, GI—iopanoic acid from in situ rat small intestine, optimal perfusion rate determined; Animals; GI-iopanoic acid from in situ rat small intestine; in situ intestinal absorption studies; Intestinal Absorption; Iopanoic Acid - metabolism; Iopanoic acid-absorption from in situ rat small intestine; Iopanoic acid—absorption from in situ rat small intestine, optimal perfusion rate determined; Male; Mathematics; Metabolic Clearance Rate; Models, pharmacokinetic—convective diffusion model, relationship between intestinal absorption clearance and intestinal perfusion rate, rats; optimal perfusion rate determined; Perfusion; Perfusion rate-optimum; Perfusion rate—optimum, in situ intestinal absorption studies, rats; Pharmaceutical Preparations - metabolism; pharmacokinetic-convective diffusion model; Rats; relationship between intestinal absorption clearance and intestinal perfusion rate; Space life sciences
• ISSN: 0022-3549; 1520-6017
• DOI: 10.1002/jps.2600700303

Iopanoic acid was used as a model compound to study the effects of the intestinal perfusion rate on the mean absorption clearance. Absorption of iopanoic acid followed first-order kinetics, with a first-order absorption rate constant (ka) linearly dependent on the dry intestinal weight. An absorption clearance-time plot revealed three phases. Phase I represented an equilibration phase, Phase II was a uniform phase, and Phase III was a physiological deterioration of the animal under prolonged anesthesia. The variability in the observations during Phase II of the absorptive clearance-time profiles was assessed statistically, and the minimum occurred at 9.9 μl/sec (0.594 ml/min). The relation between the coefficient of variance (CV) and the perfusion rate is given by CV = (-5.52 × 10-5)Q3 + (2.78 × 10-3)Q2 - (3.87 × 10-2)Q + 0.243, where Q is the perfusion rate through the intestinal lumen. These studies demonstrate that an optimal flow rate exists for minimizing the variability in in situ absorption studies. The dependency of the absorption clearance on the intestinal perfusion rate appears to conform to the convective diffusion model.