Inulin Disposition Following Intramuscular Administration of an Inulin/Poloxamer Gel Matrix

Abstract

The disposition of inulin in rats was characterized following the administration of an i.v. solution, an i.m. solution, and an i.m. injectable gel (25% w/w poloxamer 407). Blood activity levels of tritiated inulin were followed over a 6-hour time period for all intravenous (i.v.) and intramuscular (i.m.) formulations. Following i.v. solution administration, a biexponential equation was required to characterize the disposition of inulin from the blood. The total blood clearance was approximately 1.5 mL/min/100 gm body weight. This value, when converted to plasma clearance. Clp /F, (0.807 ± 0.100 mL/min/100 gm, n = 13), was within the range of values reported for the glomerular filtration rate (GFR) in rats (range 0.55 to 1.2 mL/ min/100 gm body weight). The plasma clearance of inulin following administration of an i.m. solution (0.928 ± 0.173 mL/min/100 gm, n = 9) was in close agreement to the value observed following administration of an i.v. solution. The plasma clearance of inulin following i.m. administration of the inulin/poloxamer gel formulation containing 25% w/w poloxamer 407, however, was markedly reduced (0.316 ± 0.222 mL/min/ 100 gm, n = 8). A similar reduction in the value of the plasma clearance (0.309 ± 0.017 mL/min/100 gm, n = 5) was observed following administration of an inulin solution to rats which had previously (1 hour) been injected i.m. with poloxamer 407 vehicle only (25% w/w). Thus, based on this preliminary study, it appears that simultaneous administration of inulin with poloxamer 407 as a gel formulation results in an alteration of the rat kidney to efficiently clear inulin by means of glomerular filtration. Although the mechanism by which poloxamer 407 is able to alter the disposition kinetics of inulin in the rat was not elucidated, the reduced plasma clearance of inulin by glomerular filtration was shown to be a time-dependent and reversible phenomenon.