No abstract

The purpose of this study was to prepare microspheres loaded with hydrophilic drug, bupivacaine HCl using poly(D,L-lactic-co-glycolic acid) (PLGA) and poly(L-lactic acid) (PLLA). Microspheres were prepared with varying the PLGA/PLLA ratio with two different levels of bupivacaine HCl (5 and 10%) using a supercritical anti-solvent (SAS) technique. Microspheres ranging from 4-10 microm in geometric mean diameter could be prepared, with high loading efficiency. Powder X-ray diffraction (PXRD) revealed that bupivacaine HCl retained its crystalline state within the polymer and was present as a dispersion within the polymer phase after SAS processing. The release of bupivacaine HCl from biodegradable polymer microspheres was rapid up to 4 h, thereafter bupivacaine HCl was continuously and slowly released for at least 7 days according to the PLGA/PLLA ratio and the molecular weight of PLLA.

We investigated the effects of hepatic and renal impairment on the pharmacokinetics of enrofloxacin in Sprague-Dawley rats. Experimental hepatic and renal failure were induced by carbon tetrachloride (CCL(4)) and 5/6 nephrectomy, respectively. After intravenous dosing of enrofloxacin (10 mg/kg), plasma concentrations of enrofloxacin were measured using liquid chromatograph/mass spectrometry. There was no significant effect of hepatic impairment on enrofloxacin pharmacokinetics. However, renal impairment markedly prolonged elimination half life (t(1/2lambdaz)) of enrofloxacin (P < 0.05), comparing with respective control. Total body clearance (Cl(b)) and volume of distribution at steady state (V(ss)) were significantly decreased (P < 0.05) by renal impairment. In conclusion, these results suggested that renal impairment could affect the pharmacokinetics of enrofloxacin.