AIM: To investigate the effects and quantitative relations of co-administering probenecid OF different dosages on pharmacokinetics of cefaclor in rabbits and approach the possible mechanisms involved as well. METHODS: Monitor plasma and urine cefaclor concentrations. 24 male rabbits were randomly divided into 4 groups by Cefaclor 50 mg·kg-1,Cefaclor50 mg·kg-1+Probenecid 100 mg·kg-1,Cefaclor 50 mg·kg-1+Probenecid 250 mg·kg-1 and Cefaclor 50 mg·kg-1+Probenecid 625 mg·kg-1.Blood and urine samples were collected according to the regular time schedule after intragastric administration. The concentration of cefaclor in blood and urine were determined by HPLC. Pharmacokinetic parameters were calculated by DAS (Drug and Statistical) software. Measur plasma protein-binding rate of cefaclor. The experimental groups and drug dosage were same as described above. The blood sample was drawn at 1 hour after administration,and the protein-binding rate of cefaclor was determined by equilibrium dialysis. RESULTS: Within the dosages of probenecid ranged from 0-250 mg·kg-1,T1/2ka,Tmax,Cmax and AUC of cefaclor increased in accordance with increasing dosage of co-administering probenecid while CL/F and Vd/F were decreased(P＜0.01); However,when the dosage of co-administering probenecid was 625 mg·kg-1,Cmax of cefaclor strikingly decreased(P＜0.01),while AUC and CL/F maintained at the levels of those with probenecid250 mg·kg-1.In this experiment, urinary excretive peak time of cefaclor in its prototype pos tponed gradually,biological half life prolonged and urinary excretive accumulation percentage decreased obviously(P＜0.01).To the dosages of probenecid ranging from 0-250 mg·kg-1,protein-binding rate of cefaclor decreased notably(P＜0.01)going with increasing dosages of co-administration probenecid; While the dosage of co-administration probenecid reached 625 mg·kg-1,the protein-binding rate of cefaclor corresponded to that of cefaclor 50 mg·kg-1 without probenecid (P＜0.01).CONCLUSION: Co-administering probenecid can strikingly change pharmacokinetics of cefaclor and the influential degree of pharmacokinetics parameters is dependent on dosages of probenecid used in the experiment. Biological half life prolongs and urinary excretive accumulation percentage of cefaclor decreases obviously.

To guide the reasonable clinical application of modafinil (MOD), pharmacokinetics and pharmacodynamics of MOD in mice and the correlation between them were investigated. Male mice (Kunming strain) were given a single oral dose of MOD (120 mg x kg(-1)). The plasma concentration of MOD was measured by HPLC and the pharmacokinetic parameters were calculated with DAS 3.0 software. For another batch of male Kunming strain mice, their locomotor activities were recorded by an infrared ray passive sensor after a same oral dose of MOD, and the synchronization and correlation between the changes of MOD plasma concentration and the locomotor activity induced by MOD were compared and analyzed. The results showed that the plasma concentration-time curve of MOD was fitted to two-compartment open model with a first order absorption. The main pharmacokinetic parameters t1/2alpha, t1/2beta, t(max), C(max) and AUC(0-inifinity) were 0.42 h, 3.10 h, 1.00 h, 41.34 mg x L(-1) and 142.22 mg x L(-1) x h, respectively. MOD significantly increased locomotor activity and the effect lasted for about 4 h. The changes of MOD plasma concentration and the locomotor activity induced by MOD were synchronous. In conclusion, there is a significant correlation between the effect of MOD and its plasma concentration after administration of 120 mg x kg(-1) in mice.

AIM:To observe the vascular remodel-ing of eriodictyol(EDT)in spontaneously hyperten-sive rats(SHRs)by inhibiting TLR4/NF-kB signaling and to investigate the potential mechanism of ac-tion.METHODS:WKY normal control,SHRs model and EDT administration(EDT 120 mg/kg,SHRs+EDT)group were set for 20 weeks.Tail cuff method for blood BP measurement(SBP,DBP and MBP).Ul-trasonic detection of pulse wave velocity(PWV).The aortic media membrane thickness(MT)was vi-sualized by HE staining.The percentage of aortic collagen(VFC)changes were observed by MASSON staining,Serum content of TNF-α,IL-6,and IL-10 was measured by ELISA.The TNF-α,IL-6,and IL-10 mRNA changes in the aorta were detected by q-PCR.The aortic Collagen Ⅰ and Collagen Ⅲ expres-sion was observed by immunohistochemistry,WB measured the expression of aortic TGF-β1,MMP-2,MMP-9,TLR4,p-IκBa,IκBa,p-p65 and p65.RE-SULTS:After 20 weeks of EDT administration,SBP,DBP,MBP and PWV of SHRs were significantly de-creased,MT and VFC of aorta were significantly de-creased,and protein expressions of Collagen Ⅰ,Col-lagen Ⅲ,TGF-β1,MMP-2,MMP-9,TLR4,p-l Camba and p-p65 were significantly decreased.CONCLU-SION:After long-term administration of EDT could inhibit TLR4/NF-κB signaling and exert anti-inflam-matory effects,thus reducing TGF-β1,MMP-2 and MMP-9 expression,decreasing collagen content,and finally improving aortic remodeling and sclero-sis of SHRs.

OBJECTIVETo develop a HPLC method for determination of the concentration of Danshensu in rat plasma and undertake comparative pharmacokinetic study of sodium danshensu and Salvia miltiorrhiza injection in rat as well as to assess the effect of other components of Salvia miltiorrhiza injection on the pharmacokinetics of Danshensu.

METHODRats received an iv. infusion of sodium Danshensu or S. miltiorrhiza injection (equal to Danshensu 30 mg x kg(-1)). Blood samples were collected from carotid artery. Plasma concentration of Danshensu extracted with perchloric acid was measured. The pharmacokinetic parameters were calculated with DAS2.0 software.

RESULTA good linear relationship of Danshensu was obtained from the range of 0.5 to 80.0 mg x L(-1), and the lowest limit of determination was 0.2 mg x L(-1). The plasma concentration time curves of Danshensu were best fitted with two-compartment models for Danshensu itself and for Salvia miltiorrhiza injection as well. The pharmacokinetic parameters such as t1/2alpha, AUC, CL had significant differences.

CONCLUSIONThe concomitant components in Salvia miltiorrhiza injection influence the pharmacokinetic properties of Danshensu and speed up its disposition and elimination.

Animals ; Drugs, Chinese Herbal ; administration & dosage ; pharmacokinetics ; Lactates ; pharmacokinetics ; Male ; Rats ; Rats, Sprague-Dawley ; Salvia miltiorrhiza ; chemistry

AIM: To study the chronological pharmacokinetic differences of melatonin (MEL) in non-dipper spontaneously hypertensive rats (SHR). METHODS: The HPLC detection method of MEL was established, and the specificity, precision, recovery rate and stability of the method were examined. Twelve male SD rats were divided into two groups, and a single dose of MEL (20 mg/kg) was given intragastrically at either 08:00 or 20:00, respectively. Plasma samples were collected at 0, 5, 10, 15, 20, 30, 40, 60, 90, 120, 240, 360 min after drug administration, and the plasma MEL concentration was determined by fluorescence HPLC. RESULTS: The specificity, precision, recovery rate and stability of the MEL detection method established in this study were in line with the requirements of the biological analysis method guidelines, proving that the method was mature and reliable. After MEL was administered at 08:00, the T