Pharmacokinetic Profiles of Pentoxifylline and Its 5-Hydroxyhexyl Metabolite Administered by Different Doses in Goats

Abstract

This study examined dose-dependent alterations in the pharmacokinetics of pentoxifylline (PTX) and its 5-hydroxyhexyl (M-I) metabolite in goats. Goats were administered PTX intravenously at doses of 10, 20, and 40 mg/kg. PTX and M-I plasma concentrations were quantified by HPLC. The t(1/2 lambda z) values of PTX and its M-I showed significant differences between dose groups. The 40 mg/kg dose of PTX showed lower Cl-T and V-dss values compared to the 10 and 20 mg/kg doses. For PTX and M-I, higher dose-normalized AUC values were obtained at a dose of 40 mg/kg compared to other doses. Compared to other doses, high dose-normalized C0.08 was obtained for PTX at a dose of 40 mg/kg, and a low dose-normalized Cmax was obtained for M-I at a dose of 10 mg/kg. The AUC(0-lastM-I)/AUC(0-lastPTX) ratios were 8.9%, 9.6%, and 10.6% for dosages of 10, 20, and 40 mg/kg, respectively, with the maximum ratio observed at the highest dosage. The findings indicated that the pharmacokinetics of PTX and M-I at a dosage of 40 mg/kg exhibited considerable variability in goats. This information may be helpful in adjusting the dosage regimen of PTX in goats, but further studies are needed to determine dose-dependent therapeutic efficacy and safety.