Pharmacokinetics and bioavailability of two kinds of zidovudine capsules in Chinese healthy volunteers / 中国新药与临床杂志

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.

Relative bioavailability of two formulations of indinavir in Chinese healthy volunteers by reversed phase high performance liquid chromatography / 中国新药与临床杂志

AIM: To establish a method to determine the concentration of indinavir in human plasma and study indinavir bioavailability in Chinese healthy people. METHODS: In a random two-period crossover study, 18 healthy male volunteers received a single dose of indinavir capsules 800 mg of two formulations respectively.A sensitive and specific reversed phase HPLC method was developed to quantitate plasma levels of indinavir. The drug was extracted from plasma with acetonitrile. Analysis was performed on a Hy persil C18 column with a mobile phase of acetonitrile:0.01 mol · L -1 phosphate buffer(pH 5.5 ) (43: 57).The UV detector was set at 210 nm. The standard curve covered the concentration ranged from 0. 03 to 16.38 mg · L-1. RESULTS: The concentration-time curves of reference and tested formulations both fitted to a one-compartment open model. The main pharmacokinetic rameters of tested and reference formulations were (10.6 ±s 2.4) mg· L-1 and (9.8 ±2.2)mg· L-1 for cmax, (0. 71 ± 0. 19) h and (0. 8 ±0.3) h for tmax, (1.30±0.24) h and (1.31 ±0.23) h for t1/2ke, (23±6) mg·h· L-1 and (22±5) mg·h · L-1 forAUC0-10, (24±6) mg · h · L-1 and (22±5) mg · h · L-1 for AUC0-∞, respectively. Two one-sidet test and variance analysis were performed in bioequivalent assessment. No statistically significant difference was found in AUC0-10, AUC0-∞ and cmax values between the tested and reference formulations. CONCLUSION:The reversed phase HPLC is a reliable method to determine the concentration of indinavir in human plasma and the two formulations of indinavir are bioequivalent.

Specific IgG antibodies in sera in patients with penicillin allergy / 中国药理学通报

Aim To elucidate the relationship between IgG antibodies and penicillin allergy.Methods Enzyme-linked immunosorbent assay was used to examine 8 kinds of specific IgG antibodies,including major antigenic determinants:benzylpenicilloyl(BPO),ampicilloyl(APO),amoxicilloyl(AXO)and phenoxomethylpenicilloyl(PVO),and minor antigenic determinants:benzyl-penicillanyl(BPA),amoxicillanyl(AXA),ampicillanyl(APA)and phenoxomethylpenicillany(PVA),in the sera of 241 patients with penicillin allergy.Results Except BPA-IgG,levels of 7 kinds of antigenic determinants IgG antibodies were significantly higher than those of control group(P

Changes in the expressions of CD63 on basophils in patients with penicillin allergy / 中国药理学通报

Aim To evaluate the value of expressions of CD63 on basophils in diagnosing allergy to penicillins.Methods The expressions of CD63 on basophils activated with 9 kinds of antigens(PG:penicillin G,PV:phenoxomethylpenicillin,AMP:ampicillin,AX:amoxicilloyl,6-APA:6-aminopenicillanic acid,PHA:phenylacetic acid,PHOA:phenoxacetic acid,PHPG:N-(?-hydroxyphenyl)glycine,NPG:N-phenylglycine) were detected by FAST(Flow cytometric allergen stimulation test) in 43 patients with penicillins allergy.Eight types of specific IgE and IgG antibodies to penicillins were determinated by RAST and ELISA,respectively.Results The sensitivity and specificity of CD63 used as a marker in patients with penicillins allergy were 65.12% and 93.33%,respectively.Moreover,the sensitivities of CD63 and specific IgE were higher than those of specific IgG in patients with positive skin test(P

Correlation of penicillin allergy and HLA-DRB genetic polymorphism / 中国药理学通报

Aim To explore the correlationship of allergy to penicillin and HLA-DRB genetic polymorphism.Methods Sequence specific primer-polymerase chain reaction(PCR-SSP)was used to type for human leucocyte antigen-DBR(HLA-DRB)alleles in 77 patients with allergy to penicillin and 87 healthy subjects without any allergic reactions.Results Compared with control subjects,a significantly increased frequency of DR9 was present in 77 patients with allergic reactions(11.04% vs 4.02%,RR=3.24,P

Detection of specific IgE antibodies to major and minor antigenic determinants in sera of penicillin allergic patients / 中华医学杂志(英文版)

<p><b>OBJECTIVE</b>To investigate the mechanism(s) of penicillins allergic reaction.</p><p><b>METHODS</b>The radioallergosorbent test (RAST) was used to detect 9 specific IgE antibodies, including major antigenic determinants: benzylpenicilloyl (BPO), ampicilloyl (APO), amoxicilloyl (AXO), phenoxomethylpenicilloyl (PVO) and flucloxacilloyl (FLUO), and minor antigenic determinants: benzylpenicillanyl (BPA), amoxicillanyl (AXA), 6-aminopenicillanic (APA) and phenoxomethylpenicillany (PVA), in the sera of 32 penicillin allergic patients. The relationship between specific IgE antibodies and penicillins chemical structures was studied by radioallergosorbent inhibition test.</p><p><b>RESULTS</b>Nineteen of 32 patients (59.4%) were RAST positive, among whom, five cases were positive only to one or two antigenic minor determinants, and three cases were positive only to one or three major antigenic determinants. The remaining 11 patients were positive not only to major antigenic determinants but also minor antigenic determinants. In 9 specific IgE antibodies, the positive rate of PVA-IgE was the highest (34.38%), followed by BPO-IgE (31.25%). The positive rate of FLUO-IgE was the lowest (15.63%). Of the total patient group, 53.13% were positive to one or more minor antigenic determinants, while 37.5% (12/32) were positive to one or more major antigenic determinants. The percentage of patients with urticarial reactions who were positive to minor antigenic determinants (63.16%) was significantly higher than observed in the anaphylactic shock group (38.5%, P < 0.05).</p><p><b>CONCLUSIONS</b>The minor antigenic determinant was important in allergic reaction. The combining sites of the specific IgE antibodies were likely to be the side-chain of drug or the overwhelming drug molecule.</p>

Correlation of HLA-DRB genetic locus with penicillin-specific IgE antibodies / 中国药理学通报

Aim To explore the correlation of positive specific IgE antibodies with penicillin allergy and HLA-DRB genetic polymorphism.Methods Sequence specific primer-polymerase chain reaction(PCR-SSP) was used to type human leucocyte antigen-DBR(HLA-DRB) alleles in 80 patients with positive IgE antibodies to penicillin and 101 healthy subjects without any allergic reactions.Results When different penicillin antigens were analyzed separately,the gene frequencies of DR16 in patients with positive BPO-IgE antibody and DR14.1 in patients with positive PVO-IgE antibody were found greatly lower than those of the control subjects(0 vs 8.62%,P

Correlation between allergy and HLA genetic polymorphism / 中国药理学通报

Allergy increasingly threatens human health. At present, the molecular mechanisms of allergy have been one of the hot topics. It is believed that genetic factor and environmental factor play important roles in allergy. It is not surprising that particular HLA (human leukocyte antigen) class II alleles have been implicated in susceptility to allergic diseases and in restriction of the IgE responses to a variety of allergens. It will provide an original measure if the correlation between allergy and HLA genetic polymorphism was illuminated.