The Use of a Perfluorochemical Emulsion as a Vascular Perfusate in Drug Absorption

Abstract

In-vitro simultaneous luminal and vascular perfusion using the perfluorochemical emulsion, FC-43 emulsion, as a vascular perfusate, was examined for drug absorption in rat jejunum. The intestinal membrane in this system was found to retain its normal barrier functions for drug transport, as evident from the following: (i) stable absorption clearance of tritiated water and salicylic acid at steady-state, (ii) agreement of this clearance with that by in-situ single-pass luminal perfusion, (iii) active transport of D-glucose and its inhibition by phloridzin and (iv) normal glutamate pyruvate transaminase activity in the intestinal mucosa. FC-43 emulsion gave a more normal absorption site blood flow than the usual vascular perfusate containing erythrocytes and albumin in Krebs-Henseleit bicarbonate buffer solution. Consequently, this emulsion was useful for examining the contribution of blood flow resistance toward drug absorption. The rate-limiting steps of absorption of tritiated water, antipyrine and salicylic acid were examined by perfusion using FC-43 emulsion. The absorption of tritiated water was almost completely blood flow-limited and its absorption clearance may possibly be an approximated absorption site blood flow. The contribution of blood flow resistance to total resistance for antipyrine absorption exceeded that for salicylic acid absorption.

The in-situ absorption of antipyrine as a measure of intestinal blood flow in Fluosol-DA haemodiluted rats

“…Doluisio et al(1969) reported that water flux was less than 10% absorption rates were reproducible regardless of the initial lumen concentration, and redistribution of drugs back into the lumen was undetectable. The procedure was also used by Takahashi et al (1988) who investigated antipyrine absorption as a function of flow using Fluosol-43 as a vascular perfusate. Other investigations have studied the influence of PFC emulsions on intestinal morphology or absorption.…”

“…This investigation determines if Fluosol haemodilution alters intestinal blood flow, using antipyrine in-situ intestinal absorption as the marker. Antipyrine intestinal absorption has been shown to be flow limited in unexchanged (Winne 1978;Schulz & Winne 1987) or Fluosol-43 perfused rats (Takahashi et al 1988). Antipyrine absorption was studied a t various times after haemodilution since Fluosol is eliminated slowly (Lutz & Stark 1987) and hepatic blood flow was altered in a time-dependent manner in the rat (Shrewsbury et al 1987).…”