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.(ABSTRACT TRUNCATED AT 250 WORDS)