ABSTRACT
AIM: The pharmacokinetics and biodistribution of cisplatin encapsulated in polyphase liposome (KM-1) were compared with those of free drug in rats. METHODS: The platinum levels in serum and normal organs, after a single dose of iv injection of free or encapsulated cisplatin to rats, were determined by induced coupled plasma atomic emission spectrometry. RESULTS: Serum platinum concentration-time curve after a single iv dose of KM-1 4.5 mg/kg in rats was fitted with an open three-compartment model. The pharmacokinetic parameters were as follows: Vc=0.10 L/kg, T1/2pai=0.3 h, T1/2alpha=3.5 h, T1/2beta=2.7 h, AUC=265 mg.h.L(-1), and CL(s) =0.02 g.L.h(-1). KM-1 was cleared from the circulation much more slowly than free cisplatin. Liver and spleen had the highest concentration of platinum after KM-1 treatment. CONCLUSION: KM-1 remained in the bloodstream longer than its free drug, and was taken mainly by the reticuloendothelial system.
Subject(s)
Antineoplastic Agents/pharmacokinetics , Cisplatin/pharmacokinetics , Animals , Antineoplastic Agents/administration & dosage , Cisplatin/administration & dosage , Drug Carriers , Injections, Intravenous , Liposomes , Liver/metabolism , Male , Platinum/analysis , Platinum/blood , Rats , Rats, Wistar , Spleen/metabolism , Tissue DistributionABSTRACT
A simple and novel flow injection method for the determination of gaseous SO(2) is described based on gas permeation denuder (GPD) online sampling and preconcentration. The GPD is easily prepared with poly(vinylidene) difluoride microporous membrane as gas permeable material and two Perspex blocks with smooth and flat interface and rectangular engraved channels of mirror image. The sample gas is on one side of the membrane and phosphate buffer of pH 7.0 as the absorbing solution is on the other side. Gaseous SO(2) permeates partially through the gas permeable membrane and dissolves in the absorbing solution. After preconcentration for 5.0 or 8.0 min, the solution is injected into the flow of 5.0 x 10(-4) mol L(-1) 5,5'-dithiobis(2,2'-dinitrobenzoic acid) (DTNB) in 0.025 mol L(-1) phosphate buffer. The resulting product formed between DTNB and absorbed SO(2) is spectrophotometrically monitored at 410 nm with a charge coupled device (CCD) fiber optic spectrometer. The calibration graphs for preconcentration of 5.0 and 8.0 min are linear up to 4.0 and 3.2 mg m(-3) with detection limits of 50 and 35 micro g m(-3), respectively. The corresponding analysis speeds are 8.5 and 6 samples h(-1). The method is selective and just suffer from interference of hydrogen sulfide at higher than 1% of SO(2) level (in m/V) with an error >+10%. The assay just uses cheap and common membrane and reagents and shows potential application in the monitoring of atmospheric SO(2).
