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1.
Melanie S. Joy Kimberly Dornbrook-Lavender Joyce Blaisdell Tandrea Hilliard Tammy Boyette Yichun Hu Susan L. Hogan Corina Candiani Ronald J. Falk Joyce A. Goldstein 《European journal of clinical pharmacology》2009,65(9):947-953
Background Losartan is used for anti-proteinuric as well as blood pressure effects in chronic kidney disease (CKD). It is metabolized
by cytochrome P450 (CYP) 2C9 to active E-3174. Single nucleotide polymorphisms in CYP2C9 that reduce catalytic activity could reduce clinical benefits.
Aim The study aims were to determine whether CYP2C9 variant alleles (*2 and *3) altered urinary protein excretion, glomerular filtration rate, and blood pressure in Caucasian patients prescribed losartan.
Methods Differences between baseline and 6-month follow-up outcomes were compared by CYP2C9 genotypes in 59 patients using unpaired t test or Mann–Whitney U test.
Results Primary renal disease patients had a trend toward less favorable antiproteinuric response (−31.7 ± 156 vs. −125 ± 323%; p = 0.123) when carrying variant alleles. Patients with secondary renal diseases had less favorable diastolic blood pressure
(9.8 ± 16.0 vs. −3.2 ± 10.6 mmHg; p = 0.043) and systolic blood pressure (16.2 ± 27.1 vs. −5.5 ± 17.5 mmHg; p = 0.044) with CYP2C9 variants.
Conclusion These preliminary results suggest a possible influence of CYP2C9 genotype on proteinuria and blood pressure in Caucasian CKD patients treated with losartan. 相似文献
2.
Ying Zhao Desheng Zhai Hui He Tingting Li Xijing Chen Hui Ji 《European journal of clinical pharmacology》2009,65(6):579-584
Purpose Our objective was to study the effects of polymorphic the CYP3A5 (allele *1 and *3), MDR1 [single nucleotide polymorphisms (SNPs) G2677T, C3435T] and CACNA1C (SNPs rs2239128, rs2239050, rs2238032) genes on nimodipine oral disposition and response in healthy Chinese subjects.
Methods Pharmacokinetics and pharmacodynamics data were obtained from a bioequivalence study, and the same 20 subjects were genotyped
for CYP3A, MDR1 and CACNA1C. An additional 41 healthy Chinese subjects were recruited to obtain an indication of the distribution of CACNA1C polymorphisms in the Chinese population. Racial differences in the frequency of CACNA1C alleles were assessed. The phenotype differences between genotypes were analyzed.
Results The allelic frequencies of rs2239050 and rs2238032 in our Chinese cohort were different from those in a Caucasian population
(p < 0.01). Subjects with mutant alleles (*3/*3) of the CYP3A5 gene had a decreased oral clearance of nimodipine, with a higher lnCmax or compared with those subjects with the heterozygote (*1/*3) or wild type (*1/*1) gene. The CACNA1C rs2239128 C and rs2239050 G SNPs were associated with a stronger efficacy compared with their respective alleles, rs2239128
T and rs2239050 C. MDR1 polymorphisms showed no significance in terms of nimodipine disposition.
Conclusions The polymorphic CYP3A5 (allele *1 and *3) and CACNA1C genes have effects on nimodipine oral disposition and response in healthy Chinese subjects. The homozygous variant of CYP3A5 (*3/*3) was associated with significantly increased nimodipine exposure. CACNA1C SNPs rs2239128 C and rs2239050 G were associated with a stronger efficacy. 相似文献
3.
Shigeru Satoh Mitsuru Saito Takamitsu Inoue Hideaki Kagaya Masatomo Miura Kazuyuki Inoue Atsushi Komatsuda Norihiko Tsuchiya Toshio Suzuki Tomonori Habuchi 《European journal of clinical pharmacology》2009,65(5):473-481
Purpose We assessed reported associations of CYP3A5 *1 allele with a delay in achieving target tacrolimus concentrations, and occurrence of biopsy-confirmed subclinical acute rejection
(SAR) and chronic allograft nephropathy (CAN) in Japanese subjects.
Methods Forty-one renal allograft recipients were studied. The targeted tacrolimus trough concentrations were 20–25 ng/mL up to 2 weeks
post-transplantation, 10–15 ng/mL up to 6 weeks, and 5–10 ng/mL thereafter. At 1 month and 1 year post-transplantation, allograft
biopsies were performed.
Results The CYP3A5 *1/*1 + *1/*3 (expresser) and *3/*3 (nonexpresser) alleles were detected in 19 and 22 patients, respectively. Although the mean trough concentrations were lower
in CYP3A5 expressers than nonexpressers for the first 3 weeks, no difference in frequency of SAR among CYP3A5 genotypes was found. The mean trough concentrations were lower from 8 to 12 months post-transplantation, and the frequency
of CAN was lower in CYP3A5 expressers.
Conclusions In contrast to the previous reports, the CYP3A5 *1 allele was not associated with the frequency of SAR or CAN, suggesting that further studies of different immunosuppressive
strategies using tacrolimus are needed to confirm the adequate dosing and concentration of tacrolimus for each CYP3A5 genotype. 相似文献
4.
Purpose Recent studies suggest that polymorphisms in human carbonyl reductase 3 (CBR3) influence the pharmacodynamics of doxorubicin. First, we sought to identify the promoter of CBR3. Next, we examined whether two CBR3 promoter polymorphisms (CBR3 -725T>C and CBR3 -326T>A) dictate promoter activity and hepatic CBR3 mRNA levels.
Methods The promoter activities of CBR3 reporter constructs were investigated in HepG2 and MCF-7 cells. CBR3 mRNA levels were documented in 95 liver samples from white (n = 62) and black (n = 33) donors. Genotype-phenotype correlation analyses were used to determine the impact of the CBR3 -725T>C and CBR3 -326T>A polymorphisms on hepatic CBR3 mRNA levels.
Results We identified the promoter of human CBR3. Liver samples from black donors showed higher relative CBR3 mRNA levels than samples from whites (CBR3 mRNAblacks = 3.0 ± 3.1 relative fold vs. CBR3 mRNAwhites = 1.6 ± 1.5 relative fold, p = 0.021). The variant -725C and -326A alleles did not modify the gene reporter activities of engineered CBR3 promoter constructs. In line, hepatic CBR3 mRNA levels were not associated with CBR3 -725T>C and CBR3 -326T>A genotype status.
Conclusions These studies provide the first insights into the regulation and variable hepatic expression of polymorphic CBR3. 相似文献
5.
Li-Jun Yang Lan Fan Zhao-Qian Liu Yan-Mei Mao Dong Guo Li-Hui Liu Zhi-Rong Tan Liang Peng Chun-Ting Han Dong-Li Hu Dan Wang Hong-Hao Zhou 《European journal of clinical pharmacology》2009,65(6):601-608
Objective To investigate the interaction between allicin and omeprazole and to observe the effects of allicin on CYP2C19 and CYP3A4
activity in healthy Chinese male volunteers with different CYP2C19 genotypes.
Methods Eighteen subjects (six CYP2C19*1/CYP2C19*1, four CYP2C19*1/CYP2C19*2, two CYP2C19*1/ CYP2C19*3, and six CYP2C19*2/ CYP2C19*2) were enrolled in a two-phase randomized crossover trial. In each phase, all subjects received placebo or a 180 mg allicin
capsule once daily for 14 consecutive days. The pharmacokinetics of omeprazole (20 mg orally on day 15) was determined for
up to 12 h following administration by high-performance liquid chromatography.
Results In carriers of the CYP2C19*1/CYP2C19*1 and CYP2C19*1/CYP2C19*2 or *3 genotype, allicin treatment increased the peak plasma concentration (Cmax) of omeprazole by 49.7 ± 7.2 (p < 0.001) and 54.2 ± 9.2% (p < 0.001), and increased the area under the plasma time–concentration curve ( ) of omeprazole by 48.1 ± 9.0 (p = 0.001) and 73.6 ± 26.7% (p < 0.001), respectively. The ratio of of 5-hydroxyomeprazole to omeprazole (a marker for CYP2C19 activity) decreased significantly (p < 0.001 and p = 0.001, respectively). However, no pharmacokinetic parameters were significantly changed by allicin in CYP2C19*2/CYP2C19*2. The Cmax and of omeprazole sulfone were unchanged in all three genotypes.
Conclusions Allicin reduced the metabolism of omeprazole by inhibiting CYP2C19 activity in individuals with the CYP2C19*1/CYP2C19*1 and CYP2C19*1/CYP2C19*2 or *3 genotypes, but not in those with the CYP2C19*2/ CYP2C19*2 genotype. Allicin did not significantly affect the activity of CYP3A4 in all subjects. 相似文献
6.
Objectives The aims of this study were to characterize the population frequency of PEPT2 (SLC15A2) polymorphic variants in three Asian ethnic populations, namely Chinese, Malay and Asian Indian, and to investigate the associations
of ethnicity (Chinese vs. Asian Indian), PEPT2 haplotype and cephalexin pharmacokinetics in healthy Asian subjects.
Methods
PEPT2 polymorphisms were screened from a cohort of 96 Chinese, 96 Malay and 96 Asian Indian subjects. Cephalexin (1000 mg, orally)
pharmacokinetics was characterized in an additional 15 Chinese and 15 Asian Indian healthy subjects. These 30 subjects were
subsequently genotyped for their PEPT2 polymorphisms.
Results In total, ten common single nucleotide polymorphisms (SNPs) were detected in the three populations, forming two PEPT2 haplotypes. There were significant ethnic differences in PEPT2 haplotype distribution: the frequencies of the *1 and *2 alleles were 0.307 and 0.693 in the Chinese population, 0.495 and
0.505 in the Malay population and 0.729 and 0.271 in Asian Indian population, respectively. The C
max of cephalexin was significantly lower in the Chinese (29.80 ± 4.09 μg ml−1) population than in the Asian Indian one (33.29 ± 4.97 μg ml−1; P = 0.045). This difference could be explained by the higher average body weight of the Chinese population. There was no other
significant difference in cephalexin pharmacokinetics between either ethnic or PEPT2 genotype groups.
Conclusion
PEPT2 polymorphism distributions differ significantly between Chinese, Malay and Asian Indian populations. However, cephalexin
pharmacokinetics is not meaningfully different between Chinese and Asian Indians. The association between the PEPT2 haplotype and cephalexin pharmacokinetics could not be confirmed, and future studies under better controlled conditions are
needed. 相似文献
7.
Chise Kodaira Mitsushige Sugimoto Masafumi Nishino Mihoko Yamade Naohito Shirai Shinya Uchida Mutsuhiro Ikuma Shizuo Yamada Hiroshi Watanabe Akira Hishida Takahisa Furuta 《European journal of clinical pharmacology》2009,65(6):593-600
Background and aims The effect of multidrug resistance transporter gene 1 (MDR1) on the bioavailability and kinetics of several substrates has not yet been fully elucidated. We evaluated the influence
of MDR1 C3435T polymorphism on the pharmacokinetics and pharmacodynamics of lansoprazole in Japanese subjects.
Methods Fifteen healthy volunteers with the rapid extensive metabolizer genotype of CYP2C19 were classified into three MDR1 C3435T genotype groups: C/C (n = 5), C/T (n = 5), and T/T (n = 5). Lansoprazole 30 mg was administered orally for 15 days. The intragastric pH and plasma lansoprazole levels were determined
on days 1 and 15.
Results On day 1, the mean Cmax of lansoprazole in the T/T group was significantly higher than that in the C/C or C/T groups (T/T 1,248, C/C 618, C/T 607 ng/ml;
P = 0.038). On day 15, similar MDR1 genotype-dependent differences were observed in the Cmax of lansoprazole, although smaller than the differences observed on day 1. In contrast, the intragastric pH attained after
lansoprazole administration did not differ among MDR1 genotype groups on either day 1 or day 15.
Conclusion Although the sample size was small, our study demonstrated that the MDR1 C3435T polymorphism influenced the pharmacokinetics, but not the pharmacodynamics (i.e., intragastric pH), of lansoprazole
in rapid metabolizers of CYP2C19. 相似文献
8.
Objective UDP-glucuronosyltransferases (UGTs) UGT1A9 and UGT2B7 are involved in the metabolism of antimalarial dihydroartemisinin and
antiretroviral zidovudine. Our aim was to analyze the prevalence of UGT1A9 (chromosome 2) and UGT2B7 (chromosome 4) nonsynonymous single nucleotide polymorphisms (SNPs) in West African (WA), Papua New Guinean (PNG), and North
American (NA) populations.
Methods Using a post-PCR ligation detection reaction-fluorescent microsphere assay, frequencies of UGT1A9 (8G > A, 98T > C, 766G > A) and UGT2B7 (211G > T, 802C > T, 1192G > A) SNPs were determined in WA (n = 133, 5 countries), PNG (n = 153), and NA (n = 350, 4 ethnic groups) individuals.
Results The UGT1A9 variant alleles were not common in the study populations. None of the SNPs were present in WA and PNG. Among NA, all 3 SNPs
were present (1% each) in Asian-Americans, while 98T > C was present only in Caucasian-Americans (1%) and Hispanic-Americans
(1%). Regarding UGT2B7 SNPs, the prevalence of 802C > T was 21% in WA, 28% in PNG, and 28–52% in NA. The SNP 211G > T was present only in Asian-Americans
(9%) and Hispanic-Americans (2%), while 1192G > A was not present in any of the subjects. No significant linkage was observed
at UGT1A9, UGT2B7, and between both the loci in any of the study populations.
Conclusions Taken together, the UGT1A9-UGT2B7 polymorphism profile in WA and PNG populations is similar to African-Americans, but different from Asian-Americans. It is
important to determine if these differences, along with previously reported differences in cytochrome P450 2B6 allele frequencies, are associated with altered metabolism/effectiveness of artemisinin drugs.
Electronic supplementary material Supplementary material is available in the online version of this article at and is accessible for authorized users. 相似文献
9.
Ghotbi R Christensen M Roh HK Ingelman-Sundberg M Aklillu E Bertilsson L 《European journal of clinical pharmacology》2007,63(6):537-546
Objectives To investigate the CYP1A2 genotype-phenotype relationship and to compare CYP1A2 genetic polymorphisms and enzyme activity in terms of the effect of smoking and oral contraceptive (OC) use in Swedes and
Koreans.
Methods CYP1A2 enzyme activity was determined in 194 and 150 healthy Swedish and Korean subjects, respectively, on the basis of the
4-h plasma paraxanthine/caffeine (17X/137X) ratio determined using high-performance liquid chromatography. Genotyping for
the −3860G>A, −2467delT, −739 T>G, −729 C>T, −163C>A and −3113A>G polymorphisms was performed by PCR-restriction fragment
length polymorphism analysis.
Results The mean 17X/137X ratio was 1.54-fold higher in Swedes than in Koreans (mean difference: 0.16; 95% CI of the mean difference:
0.12, 0.20; p < 0.0001). Smokers had a significantly higher 17X/137X ratio (higher CYP1A2 activity) than non-smokers, while Swedish OC
users had a significantly lower 17X/137X ratio than non-users (mean difference: 0.31, 95% CI of the mean difference: 0.23,
0.39; p < 0.0001). No effect of gender differences on enzyme activity was observed. Four known (CYP1A2*1A, *1D, *1F, and *1L) and two novel haplotypes (CYP1A2*1V and CYP1A2*1W) were found. CYP1A2*1K was rare in Swedes and absent in Koreans. No significant genotype-phenotype relationship was observed, with the exception
of CYP1A2*1F in Swedish smokers, where it was associated with higher enzyme inducibility (p = 0.02). Koreans displayed a significantly lower mean 17X/137X ratio than Swedes having the same CYP1A2 genotype, smoking habit and OC use.
Conclusions We found significant differences in CYP1A2 enzyme activity between Swedes and Koreans that could not be explained by environmental
factors or the CYP1A2 haplotypes examined, despite differences in allele frequencies. None of the investigated CYP1A2 haplotypes are critical in inducing variations in enzyme activity, with the exception of CYP1A2*1F. 相似文献
10.
Goryachkina K Burbello A Boldueva S Babak S Bergman U Bertilsson L 《European journal of clinical pharmacology》2008,64(12):1163-1173
11.
Rauwolfia vomitoria (RV) Afzel (Apocynaceae) is a medicinal plant used in traditional medicinal practice for the treatment of hypertension. This
research is devoted to phytochemical constituents, in particular, some specific alkaloids present in the RV root extract.
The phytochemical evaluation revealed the presence of alkaloids, tannins, saponins, and flavonoids in this extract. The antioxidant
activity of the RV root extract was also evaluated in a series of in vitro assays involving free radicals. The extract exhibited significant hydrogen peroxide scavenging effect relative to ascorbic
acid (p < 0.05, IC50 = 98 μg/ml), nitric oxide scavenging effect (50.37 ± 0.4% after 150 min), and metal chelating activity (89.08 ± 2.62%). In
addition, it exhibited significant ferric reducing power relative to ascorbic acid (p < 0.05). The total content of phenolic substances was 233.3 ± 2.9 mg/g. The extract was also studied for its inhibitory capacity
on lipid peroxidation as a possible mechanism of its aphrodisiac effect, by measuring thiobarbituric acid reactive substances
in various male-cow tissues incubated in a 5% solution of the RV root extract, distilled water, and antioxidant vitamins C
and E upon keeping the samples frozen for 35 days. Tissues incubated in the test solution had lower levels of malondialdehyde
(MDA) compared to those in the samples incubated in distilled water. Results obtained from this study indicate that the RV
root extract can be a potential source of natural antioxidants. 相似文献
12.
Objective Clopidogrel is activated by cytochrome P450 3A (CYP3A) to generate an active metabolite that inhibits adenosine diphosphate
(ADP)-induced platelet aggregation through irreversible binding to the platelet P2Y12 receptor. The objective of this study
was to assess the effect of the CYP3A5 genotype on the pharmacokinetics and antiplatelet effect of clopidogrel in healthy subjects.
Methods Twenty-two healthy subjects (CYP3A5*1/*1, n = 6; CYP3A5*1/*3, n = 8; CYP3A5*3/*3, n = 8) were recruited. After the administration of a loading dose of 300 mg of clopidogrel followed by 75 mg once daily for
6 days, plasma concentrations of clopidogrel and SR26334, an inactive metabolite, were measured for 24 h. The antiplatelet
effect of clopidogrel was also measured, by determining the inhibition of ADP-induced platelet aggregation for 168 h, according
to CYP3A5 genotype.
Results Mean plasma concentration profiles of clopidogrel and SR26334 were comparable between CYP3A5 genotype groups. In addition, the CYP3A5 genotype did not affect the pharmacokinetics of either clopidogrel or SR26334. CYP3A5 genotype also did not modulate the inhibitory effect of clopidogrel on platelet aggregation.
Conclusion The CYP3A5*3 genotype plays a minor role in causing interindividual variability of the disposition of clopidogrel and its antiplatelet
effect in humans. 相似文献
13.
Dorado P Cavaco I Cáceres MC Piedade R Ribeiro V Llerena A 《European journal of clinical pharmacology》2008,64(10):967-970
Purpose CYP2C8 seems to be involved in diclofenac 5-hydroxylation, while, in vitro, the 4′-hydroxylation and 3′-hydroxylation seem
to be mediated mainly by CYP2C9. We have demonstrated the relevance of CYP2C9 genotypes for diclofenac 4′-hydroxylation in healthy volunteers, so that the present study was aimed at analyzing the role
of both CYP2C8 and CYP2C9 genotypes on diclofenac metabolism, as well as determining the CYP2C8 allele frequencies and their relationship with CYP2C9 variants.
Methods A group of 142 healthy white Spanish volunteers was studied. Previously, 102 of these subjects had been phenotyped with diclofenac
and genotyped for CYP2C9. The CYP2C8 genotypes were determined by allele-specific PCR-RFLP methods. The urinary concentrations of diclofenac and its main metabolites
were analysed using an HPLC-UV method after the administration of a single oral dose of diclofenac as described previously
for part of the population studied here.
Results The diclofenac/5-hydroxydiclofenac urinary concentration ratio was higher in individuals carrying a CYP2C8*3 or CYP2C8*4 allele than in those homozygous for wild-type allele CYP2C8*1 (P < 0.05). Moreover, approximately 93% of the subjects with a CYP2C8*3 allele also carried a CYP2C9*2, and 80% of the subjects that had CYP2C9*2 variant also carried a CYP2C8*3. In addition, the four CYP2C9*2/*2 individuals were CYP2C8*3/*3.
Conclusions This is the first study showing the influence of CYP2C8 genotypes on diclofenac metabolism in vivo. The linkage disequilibrium between CYP2C8*3 and CYP2C9*2 alleles was confirmed in this Spanish population. 相似文献
14.
Hendset M Hermann M Lunde H Refsum H Molden E 《European journal of clinical pharmacology》2007,63(12):1147-1151
Objective Aripiprazole is an atypical antipsychotic drug which is metabolized by the polymorphic enzyme cytochrome P450 2D6 (CYP2D6).
The aim of the present study was to investigate the impact of the CYP2D6 genotype on serum concentrations of aripiprazole (ARI) and to determine the sum of ARI and the active metabolite dehydroaripiprazole
(DARI) in psychiatric patients.
Methods Data on steady-state serum concentrations and the CYP2D6 genotypes of patients treated with ARI were extracted from a routine therapeutic drug monitoring database. The 62 patients
included in the analysis were stratified into the following subgroups according to CYP2D6 genotype: *1/*1 (homozygous extensive metabolizers, EMs; n = 37), *1/*3–6 (heterozygous extensive metabolizers, HEMs; n = 17) and *3–6/*3–6 (poor metabolizers, PMs; n = 8). Dose-adjusted serum concentrations (C/D ratios) of ARI and ARI + DARI were compared between the subgroups.
Results The median serum concentration of ARI was 1.7-fold higher in PMs than in EMs (45.5 vs. 26.3 nM/mg, p < 0.01). The observed serum concentration of the active sum of ARI + DARI was 1.5-fold higher in PMs than in EMs (53.9 vs.
37.0 nM/mg, p < 0.05). Numerical differences in serum concentrations between HEMs and EMs were less pronounced, but statistically significant
for both ARI (p < 0.05) and ARI + DARI (p < 0.05).
Conclusion The present study demonstrates that serum concentrations of both ARI and the active sum of ARI + DARI in psychiatric patients
were significantly affected by CYP2D6 genotype. The observed differences in median C/D ratios indicate that PMs typically need 30–40% lower doses to achieve a
similar steady-state serum concentration as EMs. 相似文献
15.
Santos MM Vieira-da-Motta O Vieira IJ Braz-Filho R Gonçalves PS Maria EJ Terra WS Rodrigues R Souza CL 《Journal of natural medicines》2012,66(2):354-356
The inhibitory effects of the ethyl acetate extract and capsaicin (1) and dihydrocapsaicin (2) isolated from fruits of Capsicum annuum chili pepper type, and synthetic capsaicinoid derivatives (N-(4-hydroxyphenylethyl)decamide (3), (E)-N-(4-hydroxy-3-methoxybenzyl)-3,7-dimethylocta-2,6-dienamide (4), 4-hydroxy-3-methoxy-N-((E)-3,7-dimethylocta-2,6-dienyl)benzamide (5) and N-(4-hydroxy-3-methoxybenzyl)decamide (6) at different concentrations were evaluated against Streptococcus mutans. The minimum inhibitory concentration at which the ethyl acetate extract prevented the growth of S. mutans was 2.5 mg/mL; those of the isolated compounds 1 and 2 were 1.25 μg/mL, while 3 was 5.0 μg/mL, and 4, 5 and 6 were 2.5 μg/mL, respectively. 相似文献
16.
Toshihiro Nohara Ai Nakano Mona El-Aasr Tsuyoshi Ikeda Hiroyuki Miyashita Hitoshi Yoshimitsu Kotaro Murakami 《Journal of natural medicines》2010,64(4):510-513
We investigated the constituents of Veronicastrum villosulum (Miquel) Yamazaki (Scrophulariaceae), an endangered species belonging to the IA group. From the aerial parts of this plant cultivated at the
botanical garden of Sojo University, we isolated two new cucurbitacine-type glycosides, 3-O-α-l-rhamnopyranosyl-(1 → 2)-[β-d-glucopyranosyl-(1 → 3)]-β-d-glucopyranosides of 3β,25-dihydroxycucurbit-5,23(E)-diene-7-one-25-methyl ether and 3β,23-dihydroxycucurbit-5,24-diene-7-one-23-methyl ether. 相似文献
17.
Two phenylhexane derivatives (1, 2), benzoylergostane (3), N-benzoyl-l-leucine methyl ester (4), two known ergostanes, and highly degraded incisterol were isolated from fruit bodies of Agaricus blazei. Compound 3 exhibited strong cytotoxicity toward HepG2 cells (IC50 = 6.0 ± 0.33 μM). 相似文献
18.
Siriella armata (Crustacea, Mysidacea) is a component of the coastal zooplankton that lives in swarms in the shallow waters of the European
neritic zone, from the North Sea to the Mediterranean. Juveniles of this species were examined as standard test organisms
for use in marine acute toxicity tests. The effects of reference toxicants, three trace metals (Copper, Cadmium and Zinc),
and one surfactant, sodium dodecyl sulfate (SDS) were studied on S. armata neonates (<24 h) reared in the laboratory. Acute toxicity tests were carried out with filtered sea water on individual chambers
(microplate wells for metals or glass vials for SDS) incubated in an isothermal room at 20°C, with 16 h light: 8 h dark photoperiod
for 96 h. Each neonate was fed daily with 10–15 nauplii of Artemia salina. Acute (96 h) LC50 values, in increasing order, were 46.9 μg/L for Cu, 99.3 μg/L for Cd, 466.7 μg/L for Zn and 8.5 mg/L for SDS. The LC10, NOEC and LOEC values were also calculated. Results were compared with Daphnia magna, a freshwater cladoceran widely used as a standard ecotoxicological test organism. Acute (48 h) LC50 values were 56.2 μg/L for Cu, 571.5 μg/L for Cd, 1.3 mg/L for Zn and 27.3 mg/L for SDS. For all the reference toxicants studied,
the marine mysid Siriella armata showed higher sensitivity than the freshwater model organism Daphnia magna, validating the use of Siriella mysids as model organisms in marine acute toxicity tests. 相似文献
19.
Pérez Gutiérrez RM Martínez Flores A Vargas Solís R Carmona Jimenez J 《Journal of natural medicines》2008,62(3):328-331
Two abietane diterpenes were isolated from cyanobacteria Microcoleous lacustris, 20-nor-3α-acetoxyabieta-5,7,9,11,13-pentaene and 20-nor-3α-acetoxy-12-hydroxy-abieta-5,7,9,11,13-pentaene. These compounds were assayed against Staphylococcus aureus, Staphylococcus epidermidis, Salmonella typhi, Vibrio cholerae, Bacillus subtilis, Bacillus cereus, Escherichia coli, and Klebsiella pneumoniae. Both compounds showed activity against S. aureus, S. epidermidis, S. typhi, and V. cholerae, but not against the other bacteria. 相似文献
20.
Makiko Kusama Kazuya Maeda Koji Chiba Akinori Aoyama Yuichi Sugiyama 《Pharmaceutical research》2009,26(4):822-835
Purpose The *2 and *3 alleles of CYP2C9, with decreased enzymatic activity, are highly polymorphic and contribute to inter-individual differences
in pharmacotherapy of CYP2C9 substrates. Here, we sought for a simplified theoretical method to predict the pharmacokinetic
changes with minimal in vivo data.
Methods The changes in clearances of CYP2C9 substrates in subjects with these alleles were quantitatively estimated by parameters
from literature data: intrinsic metabolic clearance and the enzyme expression level of mutated CYP2C9, contribution of CYP2C9
to the CYP-mediated clearance (f
m2C9), and the contribution of the dominant metabolic pathways to the total clearance (f
h). To validate the accuracy of our prediction, the changes were compared to reported in vivo values.
Results Sufficient data were available for nine substrates: celecoxib, diclofenac, S-flurbiprofen, losartan, S-phenprocoumon, phenytoin, tolbutamide, torsemide, and S-warfarin. These predicted values, either using the intrinsic clearance specific to each substrate, or the averaged values
(*2: 0.66, *3: 0.13, (ratio to *1)), correlated well with observed values (r
2 = 0.812, 0.786, respectively).
Conclusions This theoretical method well estimated the quantitative changes in pharmacokinetics of CYP2C9 substrates in subjects with
mutated alleles of CYP2C9. This can be applied to drug development even from the early clinical phases.
Makiko Kusama and Kazuya Maeda contributed equally to this work. 相似文献