ABSTRACT
The paper is to report the study of pharmacokinetics of transdermal administered nicotine in the brain of freely moving rat by using microdialysis with stable labeled isotope as internal standard. The pharmacokinetic behavior of nicotine in Sprague Dawley rat brain was investigated after intranasal administration (3.75 mg). Brain fluid samples were collected by intracerebral microdialysis with DL-nicotine as internal standard. Concentrations of nicotine and DL-nicotine in the sample were measured by HPLC-MS/MS. Main pharmacokinetic parameters were calculated and analyzed by Das 2.0 pharmacokinetic software. The recovery of nicotine and the delivery of DL-nicotine were the same. The fate of absorption and distribution was two compartment model and the values of t1/2alpha was 170.31 min, t1/2beta was 263.30 min and the AUC(0-infinity) was 2.75 x 10(5) microg x L(-1) min separately. DL-nicotine can be used to calibrate the recovery of nicotine, and the new method of stable isotope microdialysis can be used to study the pharmacokinetics of freely moving rat. It will make sense for the treatment of addiction of tobacco and provide a new thought for the research of pharmacokinetics-pharmacodynamic combination.
Subject(s)
Animals , Female , Male , Rats , Administration, Cutaneous , Administration, Intranasal , Area Under Curve , Brain , Metabolism , Chromatography, High Pressure Liquid , Deuterium , Isotope Labeling , Methods , Microdialysis , Methods , Nicotine , Pharmacokinetics , Rats, Sprague-Dawley , Tandem Mass SpectrometryABSTRACT
The paper reports the evaluation of the feasibility of using internal standard method for the determination of nicotine recovery in microdialysis in vitro. This in vitro experiment included two conditions. Nicotine and codeine phosphate were dissolved in Ringer's solution. Nicotine, codeine phosphate and the mixture of them were perfused through the CMA30 linear probe separately to calculate the proportion of the recovery (or delivery) of nicotine to that of codeine phosphate. And then codeine was perfused through the probe which was immersed in nicotine solution with different concentrations to calculate the proportion, too. In another condition nicotine was dissolved in rat plasma. The rat plasma protein binding rate was determined by using retrodialysis and internal standard method in vitro. The results are as follows: the proportion of the recovery (or delivery) of nicotine to that of codeine phosphate was fairly stable. The delivery of codeine was independent of nicotine concentration in the external medium. Protein binding rate determined by retrodialysis was almost the same as that determined by internal standard method. It suggests that the internal standard method is an effective way in the determination of nicotine recovery and codeine phosphate can be used as the internal standard.
Subject(s)
Animals , Male , Rats , Blood Proteins , Metabolism , Chromatography, High Pressure Liquid , Methods , Codeine , Microdialysis , Methods , Nicotine , Metabolism , Protein Binding , Rats, Sprague-DawleyABSTRACT
<p><b>OBJECTIVE</b>To study bioequivalence of Sinomenine patch made by different preparation process, and to testify feasibility and superiority of microdialysis as a new method in topical bioequivalence study.</p><p><b>METHOD</b>Normal gel patch and liposome gel patch of sinomenine were prepared by different preparation, nude mouse served as the experimental subjects sampling method of drug in the skin was tissue homogenization microdialysis, and drug concentration in dialysate was determined by HPLC.</p><p><b>RESULT</b>Results of tissue homogenization showed that liposome gel patch leads more remainder drug in the skin of nude mouse than normal gel patch, and results of microdialysis showed that liposome gel patch led higher instantaneous drug concentration than normal gel patch. Concentration-time curve of sinomenine in the skin accorded with the results of most dermal delivery systems studies over the world.</p><p><b>CONCLUSION</b>Topical bioequivalence of liposome gel patch of sinomenine is higher than that of normal gel patch of sinomenine. Microdialysis can be used to study bioavailability and bioequivalence of different preparation.</p>
Subject(s)
Animals , Male , Mice , Administration, Cutaneous , Chromatography, High Pressure Liquid , Microdialysis , Methods , Morphinans , Pharmacokinetics , Skin , Metabolism , Therapeutic EquivalencyABSTRACT
<p><b>OBJECTIVE</b>To establish an HPLC method for the determination of entrapment efficiency of sinomenine liposomes.</p><p><b>METHOD</b>The liposomes and dissociated drugs were separated by sephadex filtration, mini-column centrifugation and dialysis. The methodology study and the optimization of determining condition were carried out at the same time.</p><p><b>RESULT</b>Sephadex filtration could effectively separate the sinomenine liposomes from dissociated sinomenine. The column recovery was 98.8%, the average entrapment efficiency of three tests was64.9%, RSD 2.67%.</p><p><b>CONCLUSION</b>The method was simple, exact, and had a good reappearance. It can be used to examine the entrapment efficiency of sinomenine liposomes.</p>