The Preliminary Study Of The Bio-pharmaceutics Of Oral Antibiotic Compound Preparation

Biopharmaceutics and Pharmcokinetics are the sciences which study on the in vivo law of medicine.Through reseraching on the absorption,distribution,metabolism and excretion of drug, clarifying the relation between form of drug, biological factor and drug effect, it plays a more and more important role in various respects.Etiology microbial infection account for a large part for threating human healthy. So many types antibacterial are developed to deal with it. However, antibacterial are so widely and long used that the tolerance to antibacterial of pathogens is increasing day by day, which leads to the decrease in clinical effect.Cefadroxil(CDX)is the first generation half-synthesis orally-taken antibacterial which has broad spectrum bactericidal recorded in Chinese pharmacopoeia. It has good function on many germs.But this medicine is not able to bear enzymes and can be easily destructed by P-Lactamase produced by drug resistance strain. Sulbactam and tazobactam are inreversible competitive P-Lactamase inhibitors, which can be used with many P-Lactamase antibacterials. They eliminate p-Lactamase antibacterial's degradation by inhibiting the activity of P-Lactamase, and produced transparent synergism at lower concentration.The injection combining cephalosporin antibacterial and p-Lactamase inhibitors has been widely used in clinic, which proves the important clinic significance. But no research has been reported on orally-taken preparation. The topic studys on the possibility of this kind of orally-taken c ompound preparation, and basicly focus on the problem of absorption and pharmacokinetic procedure. Wechoose cefadroxil(CX), sulbactam sodium (SB), and tazobactam (TB) as model drugs, evaluate the absorption mechanism and research the rationality of the antibacterial compound preparation designed for non-vessel administration, we create in situ perfusion in rats for single or combined model drugs to research and evaluate the drug in vivo absorption kinetic procedure. We chose beagle dog as experiment animal, study on the in vivo absorption kinetic law for single or combined model drugs, and study on the relation between the results of in vivo and intro vivo to see that if the two results are similar in the reasonability of model drugs' combination.Through many experiments, analysis method which can determine the three drugs in the same time is settled. It is accurate and reliable, can be easily and quickly handled.The results of rat in situ perfusion expermient show that perfusate concentration won't influence the absorption law of the three drugs. In concentration range examined, their absorptions a 11 show t he c haracters o f 1 inear k inetics i n digestive tract. Apparent absorption mechanism is passive diffusion. CX has good absorption .SB and TB has similar absorption parametes , but their absorption is not good. Comparing using CX with SB and employing the two drugs respertively , statistical difference can't be found in absorption law. Comparing using CX with TB and employing the two drugs respertively , statistical difference can be found in absorption law and absorption percentage per hour(P%) decreases. The results show that choosing SB and CX to compose compound preparation is better.We use beagle dog as experiment animal, study the in vivo pharmacokinetic after administer single dosage's CX and SB. Use DAS to process data and statistical analysis. Use AUCo~t^Cmax>Tmax as indexs to estimate bioequality of CX between administered alone and administered with SB. The results indicates that Cmax, Tmax are bioequality. AUCo~t is increased obviously when used with SB, which shows that absorption increases.We also compare bioequality of SB administered alone with administered with CX. The results show that pharmacokinetic characters of SB didn't change, SB is equal in bioequality when administer in the two ways.We apply Loo-Rigelman method in calculating in vivo absorption percentage, and compare it with the absorption percentage learn from rat in situ perfusion model. The results show that the two methods have significant positive correlation no matter CX is used alone or combine with SB. The results also show that the two methods have positive correlation no matter SB is used alone or combine with CX, but dependability i s not significant. So we can c onclude that rat in situ perfusion model can be used to predict in vivo absorption of CX, but not for SB. And employing two methods together to study the same drug , comprehensive comparison Can make the experiment result more reliable.The Chromatography method measuring three model drugs at the same time is settled in the research.. From applying and; evaluating the method, we can see that it satisfies the requirement of the study. And method measuring CX, SB and TB at the same time didn't reported before.The experiment results of rat in situ perfusion and in vivo experiment show that absorption of SB is influenced by species, which give a clue to us that we should pay attention to the influence on drug's availability and safe when using SB in clinic.The result of in vivo experiment shows that CX and SB can be absorbed when taken orally. After administered together ,the kinetics character of SB didn't change, and Cmax> Tmax of CX didn't change, but AUC of CX increases. The study seem to us that SB and CX have compound preparation biopharmacy foundation. The thinking and method can be referred when researching and developing new type orally-taken antibioltic compound preparation, and establish basic of biological pharmacy for the compound preparation's reasonability. The study results also show great clinic significance in enforcing antibioltic effect, enlarging antimicrobial spectrum and rising patient's compliance.