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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.
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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.
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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.
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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