Pharmacokinetics of tramadol hydrochloride in the extracellular fluid of mouse frontal cortex studied by in vivo microdialysis / 药学学报

The paper aims to explore the studying method for the pharmacokinetics of drugs in target organs, the pharmacokinetic process of tramadol hydrochloride in the extracellular fluid of frontal cortex (FrCx) of mice was investigated. Six male mice (Kunming strain) were anaesthetized (urethane, 1.8 g x kg(-1), ip) and secured on a stereotaxic frame. A microdialysis probe was implanted into the FrCx and perfused with artificial cerebrospinal fluid at a flow rate of 2 microL x min(-1). One hour later, mice were administrated (ip) with tramadol hydrochloride (50 mg x kg(-1)) and dialysates were collected continuously at 12-min intervals (24 microL each) for 6 h. The tramadol concentration in dialysates was determined by HPLC-Ultraviolet detection method, and the concentration-time curve and pharmacokinetic parameters of tramadol were calculated with DAS software. The results showed that the pharmacokinetic process of tramadol in the FrCx extracellular fluid of mice was fitted to a two-compartment open model, and the main pharmacokinetic parameters t1/2alpha, t1/2beta, t(max), C(max) and AUC(0-infinity) were (0.27 +/- 0.05) h, (2.72 +/- 0.24) h, (0.50 +/- 0.10) h, (2 110.37 +/- 291.22) microg x L(-1) and (4 474.51 +/- 441.79) microg x L(-1) x h, respectively. In conclusion, a studying method for pharmacokinetics of drugs in the target organ is established, which is simple and feasible. Tramadol hydrochloride shows a two-compartment model in the extracellular fluid of the mouse FrCx, and the distribution- and elimination half-life are 0.5 h and 2.7 h, respectively.

Pharmacokinetics--pharmacodynamics of modafinil in mice / 药学学报

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.

Tissue distribution in mice of danshensu from sodium danshensu and Salvia miltiorrhiza injection / 中国中药杂志

<p><b>OBJECTIVE</b>To determine the concentration in mice of danshensu from sodium danshensu and Salvia miltiorrhiza injection and undertake comparative study of them as well as to assess the effect of other components of S. miltiorrhiza injection on the tissue distribution of danshensu.</p><p><b>METHOD</b>Mice received intraperitoneal administration of sodium danshensu or S. miltiorrhiza injection (equal to danshensu 60 mg x kg(-1)) respectively, and was executed 30 minutes after administration. The concentration of danshensu in different tissues was separately determined by high performance liquid chromatographic method.</p><p><b>RESULT</b>The characteristic profiles of sodium danshensu in different tissues were C(kidney) > C(spleen) > C(lung) > C(heart) > C(liver). The characteristic profiles of danshensu from S. miltiorrhiza injection in different tissues were C(kidney) > C(lung) > C(spleen) > C(heart) approximately C(liver). The concentration of danshensu in S. miltiorrhiza injection in liver and kindey was higher than sodium danshensu itself.</p><p><b>CONCLUSION</b>It was suggested that the other components in S. miltiorrhiza injection influent the distribution profile in tissues of danshensu.</p>

Comparative pharmacokinetic study of sodium Danshensu and Salvia miltiorrhiza injection in rat / 中国中药杂志

<p><b>OBJECTIVE</b>To 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.</p><p><b>METHOD</b>Rats 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.</p><p><b>RESULT</b>A 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.</p><p><b>CONCLUSION</b>The concomitant components in Salvia miltiorrhiza injection influence the pharmacokinetic properties of Danshensu and speed up its disposition and elimination.</p>

Effects of co-administering probenecid orally on pharmacokinetics of cefaclor in rabbits / 中国临床药理学与治疗学

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.

Characteristics of sleep-wake cycles in mice lacking prostanoid DP receptors / 中国临床药理学与治疗学

AIM: To investigate the effect of prostanoid DP receptors (DPR) on sleep-wake regulation in mice. METHODS: Under pentobarbital anesthesia, mice were chronically implanted with electroencephalogram (EEG) and electromyogram (EMG) electrodes for polysomnographic recordings. The spontaneous sleep-wake cycles were monitored continuously by EEG/EMG recording system for 24 h beginning at 800 p.m. and analyzed by SLEEPSIGN software in DPR knock out (KO) and wild type (WT) mice. RESULTS: DPR-KO mice exhibited a similar circadian rhythm of sleep-wake cycles to WT mice. The amounts of rapid eye movement (REM) sleep or non-REM (NREM) sleep during both the light and dark periods were identical between the DPR-KO and WT mice. Whereas, an increase in the episode number of wakefulness and a shortage in the duration of NREM sleep were found in DPR-KO mice during the light period compared with WT mice. Moreover, DPR-KO mice showed lower activity in delta-wave component in NREM sleep and higher activity in theta-wave component in REM sleep than WT mice. CONCLUSION: DPR plays a crucial role in mediating the prostaglandin D2-induced sleep. Deficiency of DPR results in the low intensity and fragmented diurnal NREM sleep and the high vigilance REM sleep, with the normal circadian rhythm of sleep in mice.

Pharmacokinetics of salvia miltiorrhiza injection in rats / 中国临床药理学与治疗学

AIM: To investigate pharmacokinetics of salvia miltiorrhiza injection in rats. METHODS: A dose of salvia miltiorrhiza injection (standardized as Dhpl 40 mg?kg -1 , iv) was given in rats and plasma Dhpl concentrations were determined by a HPLC method. The 3p87 software was used to calculate the pharmacokinetic parameters of Dhpl. RESULTS: The main parameters were as follows: T 1/2? = 0.29 ? 0.23 h, T 1/2? = 1.75 ? 0.99 h, V d= 0.83 ? 0.70 L?kg -1 , Cl= 0.33 ? 0.16 L?h -1 ?kg -1 , and AUC (0-inf) =149?66 mg?h?L -1 . CONCLUSION: Data of the blood concentration time of salvia miltiorrhiza injection can be fitted to a two compartment open model.

Influence of probenecid on pharmacokinetics of cefaclor / 中国临床药理学与治疗学

AIM: To observe the effects of proben-ecid of different doses on pharmacokinetics of cefaclor and to provide the basis of their co-adiministration. METHODS: 30 rabbits were randomly divided into 5 groups: Cef 50 mg?kg -1, Cef 50 mg?kg -1+Pro 50 mg?kg -1,Cef 50 mg?kg -1+Pro 100 mg?kg -1,Cef 50 mg?kg -1+Pro 200 mg?kg -1,Cef 25 mg?kg -1+Pro 100 mg?kg -1. The blood samples were drawn from thigh vein after IG and the concentrations of cefaclor were determined by HPLC. Pharmacokinetics parameters were calculated by NDST procedure. RESULTS: In groups with Cef 50 mg?kg -1, C max and AUC of cefaclor increased, and Vd/F and Cl/F decreased progressively with the adding probenecid. There was no significant difference between Cef 25 mg+Pro 100 mg and Cef 50 mg?kg -1 in each parameter except Cl/F. CONCLUSION: Probenecid can remarkably alter the pharmacokinetics of cefaclor and the magnitude of the effects of probenecid is dependent on its dose in this trial. Cef 25 mg?kg -1 with Pro 100 mg?kg -1 can reach the same blood concentration as Cef 50 mg?kg -1 alone.