AIM: To study the pharmacokinetics of loratadine in healthy volunteers after single and multiple oral administrations of loratadine, paracetamol and pseudoephedrine (LPP) sustained-release tablets.METHODS: Twenty-four volunteers were randomized into two groups which included six men and six women in each group. In the single dose design, volunteers received either one or two tablet (s) of LPP. After 1 wk wash out period, volunteers of one tablet group participated in multiple dose design in which each volunteer received one tablet of LPP twice per day for six consecutive days. The concentrations of loratadine in plasma were determined by HPLC-MS method and the pharmacokinetic parameters were calculated. RESULTS: In the single dose design, main pharmacokinetic parameters of one and two tablet group were as follow: cmax were ( 1.5 ±groups were similar to each other. The obtained multi-dose pharmacokinetic parameters were as follows: AUCssrespectively. D (F) was (3.3 ± 0.8) %. The pharmacokinetics of loratadine was linear. There were no significant difference in pharmacokinetics between single-dose and multi-dose. CONCLUSION: The release and absorption of loratadine in experimental tablet are close to those in loratadine tablet and not affected by the other two components, pseudoephedrine and paracetamol, in LPP sustained release tablet.

AIM: To develop a simple and sensitive high-performance liquid chromatography (HPLC) for the quantification of zidovudine and to study the pharmacokinetics of two kinds of zidovudine capsules in Chinese healthy volunteers. METHODS :The concentrations of zidovudine in plasma were determined by a validated HPLC method with UV detection. A randomized two-way crossover study was conducted in 18 fasting volunteers to compare plasma pharmacokinetic profile and single-dose tolerability of a new zidovudine capsules. RESULTS: The main pharmacokinetic parameters of two formulations, reference and test capsules, were as follows: cmax were (2 252±s 837) μg·L-1 and (2 300±1 099) μg·L-1; tmax were (0.49±0.19) h and (0.5±0.3) h;t1/2 ke were (0.93±0.19) h and (0.99±0.24) h; AUC0-t were (2 530±452) μg·h·L-1 and (2 467±605) μg·h·L-1;AUC0-∞ were(2 689 ± 414) μg·h·L-1 and (2 583±575) μg·h·L-1. The results of ANOVA and two one-side t test statistical analysis for lg AUC0-t, lg AUC0-∞ and lg cmax showed that two formulations were bioequivalent. CONCLUSION:The method is convenient, sensitive, accurate and reproducible, and could be applied to determining the plasma zidovudine concentration and studying on pharmacokinetics. Two zidovudine capsules are bioequivalent in Chinese healthy volunteers.

AIM: To evaluate the efficacy and safety of neurotropin in the treatment of neuropathic pain.METHODS: A systematic literature search was performed in biomedical database including MEDLINE,EMBASE, Cochrane Central Register of Controlled Trials, CBM and CNKI. All studies focused on the clinical controlled trials, especially randomized controlled trials (RCTs) . The outcome measures included efficacy,life quality, cost of the treatment and adverse reactions. Quality assessments of clinical trials were evaluated with Jadad Score. Meta-analysis of included studies was performed with Revman software. RESULTS: Twenty-six clinical trials were included. Jadad Score of 24 trials was less than 3, which indicated the poor quality of the trials. None of the clinical trials evaluated the changes in life quality and cost related to neurotropin treatment.Meta analysis of 11 trials indicated neurotropin was more effective than placebo or blank, and the odds ratio of efficacy was 3.84 [2.68, 5.50] . The combining effect of 6 RCTs showed that neurotropin decreased the pain scores measured by Visual Analog Scale significantly compared with placebo or blank, the weighted mean difference (WMD) was -1.76 [-2.31, -1.21] . The pooled effects of the trials comparing neurotropin with other pain relieving drugs such as earbamazepine or NSAIDs also showed positive effect favored neurotropin.Neurotropin had no more adverse reactions than placebo, carbamazepine or NSAIDs, and the pooled risk difference was -0.01 [-0.04, 0.02] . CONCLUSION: According to present evidence, neurotropin may be effective and safe in the treatment of neuropathic pain. However, the poor quality of the studies decreases the persuasion of the results. Large-scale and well-designed RCTs with enough follow-ups should be carried out to provide further evidence for the use of neurotropin in neuropathie pain.

AIM: To investigate the effects of metallothionein (MT) induced by zinc on doxorubicin (DOX)-treated mice and to explore the potential mechanisms. METHODS: Male C57BL/6J mice were divided randomly into 4 groups (n = 6) following control, DOX, Zn and Zn plus DOX. Mice were pretreated with eikg-1, ip) or equal volume of saline, and were killed on d 4 after the last injection. Serum and hearts were collected for examination. RESULTS: Zinc pretreatment elevated cardiac MT levels significantly while other antioxidants in heart including glutathione (GSH), glutathione peroxidase (GSHpx) , superoxide dismutase (SOD), and catalase (CAT) were not altered. Severe oxidative injury occurred in the mice treated with DOX as myocardial lipid peroxidation and morphological changes manifested by myocardial fibers swelling and vacuolization and nuclear condensation or dissolution, with increased activities of serum creatine kinase and lactate dehydrogenase and depletion of GSH, GSHpx, and SOD while CAT activity was increased in compensation. However, pre-induction of MT with zinc attenuated all of these toxic changes significantly. Furthermore, DOX induced elevation of hydrogen peroxide in heart tissues was greatly inhibited by zinc pretreatment. CONCLUSION: Preinduction of MT by zinc protects the heart from DOX-induced cardiotoxicity, and this effect is possibly correlated with the property of MT on scavenging free radicals in vivo.

AIM: To examine the pharmacodynamics of a self-developed oral colon-specific delivery coated tablets of 4-aminosalicylic acid (4-ASA) on rats. METHODS: Ulcerative colitis rat model was developed by intrarectal administration of 2, 4, 6-trinitrobenzenesulfonic acid (TNBS) in alcohol. Rats were divided randomly into healthy control group, TNBS control group, TNBS + lower dose (coated tablets) group, TNBS +medium dose (coated tablets) group, TNBS + higher dose (coated tablets) group, TNBS + sulfasalazine (SASP) group, TNBS + medium dose non-coated tablet group. Several indices including macroscopic change,histological damage, and tissue myeloperoxidase (MPO) activity were examined after 5 consecutive oral drug administration to assess pharmacodynamics of the coated tablets. RESULTS: An experimental ulcerative colitis in rats was induced by TNBS. Compared with 4-ASA non-coated tablet group, decreased macroscopic and histological damage score and lower MPO activity were observed after the oral administration of 4-ASA coated tablets or SASP. There was no significant difference between the effects on the indices of higher dose of coated tablets and SASP (P ＞ 0.05) CONCLUSION: The self-made 4-ASA oral colon-specific delivery coated tablet showes higher effect than non-coated tablets to treat ulcerative colitis in rats.

AIM: To access the difference of the efficacy between terbinafine and itraconazole in the treatment of dermatophyte onychomycosis. METHODS: The Medline, Science Direct On Site (SDOS), and Springer database were searched in detail on the data of the mycological cure rates of the two antifungal agents for treatment of dermaphyte onychomycosis occourring in patients aged from 18 a to 60 a with the published double blind randomized clinical trials and then pooled. The odds ratio (OR) and its 95 % confidence interval (CI) were calculated. RESULTS: Six treatises of double blind randomized clinical trials were selected for this analysis according to the screening criteria. The mycological cure rate of continuous terbinafine 250 mg per day was higher than that of either therapeutic effect of itraconazole pulse 400 mg per day (OR = 5.01, 95 % CI (3.42 - 7.33)) or continuous itraconazole 200 mg per day (OR = 2.58, 95 % CI (1.91 - 3.49)) . CONCLUSION: Terbinafine is more effective than itraconazole in the treatment of dermatophyte onychomycosis.

AIM: A new HPLC-MS method was developed to determine finasteride in human plasma. METHODS: Two formulations of finasteride tablets were given to 20 healthy male volunteers according to a randomized 2-way cross-over design. The samples were extracted by ethyl acetate under basic conditions, then were separated by C18 column and determined by mass detector. RESULTS: The calibration curve of finasteride was linear and intra-day and inter-day RSD were less than 10 %. The pharmacokinetics parameters of the two formulations (4.5 ± 0.5) h for t1/2; (3.0 ± 0.7) and (2.8 ± 0.9) h for tmax, respectively. The results indicated that there was no significant difference on cmax, A UC0-24, t1/2 or tmax values between the two formulations. CONCLUTION: The relative bioavailability of tablets I with respect to tablets Ⅱ is (99.3 ± 9.2) % by the A UC0-24 measurement, and bioe quivalence is observed between the two tablets.

AIM: To determine the distribution and frequency of functionally important allelic variants in the cytochromes P450 (CYP) 2C19, arylamine N-acetyltransferase 2 (NAT2), and thiopurine S-methyltransferase (TPMT) genes in the Han Chinese population and compare them with those of other ethnic populations.METHODS: Genotyping was carried out in a total of 210 unrelated Han Chinese volunteers derived from He-nan area. CYP2C19 variants ( * 2 and * 3), NAT2 variants ( * 6 and * 7), and TPMT variants ( * 3A, * 3B, and * 3C) were detected using polymerase chain reaction/restriction fragment length polymorphism (PCR-RFLP)assays. Detection of NA T2 * 5 and TPMT * 2 were performed using allele-specific polymerase chain reaction assays. RESULTS: Allele frequencies of CYP2C19 * 2 and * 3 occurred with 34.76 % and 6.4 %, respectively.Thirty-one persons ( 14.8 % ) carried two of these CYP2C19 alleles responsible for poor metabolizing activity.The frequencies of specif ic NAT2 alleles were 59.1%, 4.1%, 26.4 %, and 9.5 % for * 4 (wild-type), * 5(341C), * 6 (590A), and * 7 (857A), respectively. Genotyping of three different single nucleotide polymorphisms in the NA T2 gene revealed that the frequency of slow acetylators was 19.5 %. TPMT * 3C had an allelic frequency of 1.2 %. TPMT* 2, TPMT * 3A, or TPMT* 3B was not detected in the analysed samples. CONCLUSION: The overview of allele distribution for drug-metabolizing enzymes CYP2C19, NAT2, and TPMT among a Han Chinese population shows obvious difference to Caucasians. The data will be useful for clinical pharmacokinetic investigation and drug dosage administration to Han Chinese population.

AIM: To discuss the effects of phytoestrogenic-genistein on cathepsin K (CK) expression stimulated by interleukin-1α (IL-1α) in osteoclast-like cells (OCLs) . METHODS: The OCLs were isolated from tissue of human giant cell tumor of bone (GCT) . The cells treated with reagents were divided into 7 groups including control (treated with phenol red-free-DMEM), vehicle (treated with 1.2 nmol· L-1 IL- 1α), 10-10-10-6genistein, genistein+ ICI 182.780, and 17[β-estrodiol (17β-E2) group. The cells were treated with 1.2 nmol· L-1IL-1α after pre-treated with genistein or 17β-E2 for 48 h (excluded the control group) . Expression of CK wasdetermined by reverse transcriptase-polymerase chain reaction (RT-PCR) and Western blot in OCLs stimulated by IL-1α in the presence of genistein or 17[β-E2. RESULTS: The obvious increase of expression of CK by IL1α in vehicle group was noted in comparing with control group (P ＜ 0.01 ) . Genistein down-regulated CK gene expression stimulated by IL-1α at the transcription level in a dose-dependent manner (r = 0.68, P ＜ 0.01 ) .Genistein down-regulated CK protein expression stimulated by IL-1α also in a dose-dependent manner (r = 0.61,P ＜ 0.01 ). The effects of genistein were abrogated partly after treatment with the estrogen receptor antagonist ICI 182.780. CONCLUSION: Genistein inhibits CK expression stimulated by IL-1α partly through estrogen receptor in OCLs.

AIM: To study the protective effects of baicalin on myocardial ischemia-reperfusion injury in rats. METHODS: The models of myocardial ischemia-reperfusion injury were established by occluding left anterior descending coronary artery (LAD) for 30 min, followed by reperfusion for 120 min. The rate of rise and decline of left ventricular pressure (±dp/dtmax) and end-diastolic pressure of left ventricle (LVEDP) were monitored continuously with polygraph. After reperfusion, the blood and myocardium samples were taken for determination of malondialdehyde (MDA) content, superoxide dismutase (SOD), Na+-K+-ATPase, Ca2+-ATPase activities in myocardium, creatine kinase (CK) and lactate dehydrogenase (LDH) in serum with spectrophotometer. The ultrastructural changes in ischemic myocardium were assessed by transmission electron microscope. RESULTS:dtmax and LVEDP, decreased plasma CK and LDH levels, reduced myocardial MDA content, and increased the activities of SOD, Na+-K+-ATPase, and Ca2+-ATPase in myocardium following ischemia-reperfusion. The ultrastructural injury in reperfused myocardium was relieved. CONCLUSION: Baicalin possesses a protective effect against myocardial ischnemia-reperfusion injury through scavenging oxide radicals and improving Na+-K+-ATPase and Ca2+-ATPase activities.