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  • 1
    Electronic Resource
    Electronic Resource
    Pharmacokinetics of ketoprofen following single oral, intramuscular and rectal doses and after repeated oral administration (1980)
    Springer
    European journal of clinical pharmacology 18 (1980), S. 407-414 
    Details
    ISSN: 1432-1041
    Keywords: ketoprofen ; pharmacokinetics ; relative bioavailability ; single doses ; repeated doses ; prediction of kinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics of ketoprofen was studied in the same healthy subjects after single oral, intramuscular and rectal doses, and after repeated oral administration. No significant difference in the mean t1/2 (1.13–1.27 h) was observed after the different modes of administration. The mean [AUC] 0 ∞ after rectal administration of a suppository showed the minimum significant difference (p〈0.05) from that after oral administration of the capsule. The apparent volume of distribution (Vd/F) was approximately 10–15% of body weight. The renal contribution (mean, 0.10–0.15 ml/min/kg) to the plasma clearance of free ketoprofen was assumed to be, at most, 8.3–12.9%. The projected cumulative excretion of total (free plus conjugated) ketoprofen via urine exceeded 63–75% of the dose, of which approximately 90% was ketoprofen glucuronide. A mean of 71–96% and 73–93% of the oral capsule was estimated to be systemically available after administration of the intramuscular preparation and rectal suppository, respectively. In four of seven subjects, CPK concentration was elevated after the intramuscular injection. The mean steady-state concentration of ketoprofen in plasma ranged from 0.43 to 5.62 µg/ml after the final dose of a 50 mg q.i.d. regimen. The disposition data and plasma levels observed at steady-state were in agreement with those predicted from the single oral dose study. The accumulation ratio was 1.08±0.08. The results suggest that the rectal suppository can be recommended as an extravascular mode of administration of this drug.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00636794
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  • 2
    Electronic Resource
    Electronic Resource
    Bioavailability and pharmacokinetics of theophylline in plain uncoated and sustained-release dosage forms in relation to smoking habit I. Single dose study (1983)
    Springer
    European journal of clinical pharmacology 24 (1983), S. 79-87 
    Details
    ISSN: 1432-1041
    Keywords: theophylline ; smoking habit ; absolute bioavailability ; pharmacokinetics ; sustained release preparation ; plain tablet preparation ; antipyrine pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The bioavailability and pharmacokinetics of theophylline from a plain uncoated and 2 newly designed, sustained-release tablet formulations, as compared to intravenous aminophylline, were studied in 12 healthy adult male volunteers. The subjects were divided into two groups (n=6) with respect to smoking habit and on 4 separate occasions each received, on a randomized cross-over basis, a single dose of 400 mg equivalent of theophylline from every dosage form. The intravenous aminophylline study showed that habitual smoking had a significant (p〈0.05) effect on plasma theophylline clearance (0.051±0.006 vs 0.035±0.004 l/kg/h). Smoking significantly reduced the raw AUC from the 4 dosage forms (p〈0.05), but did not change the characteristics of absorption of each formulation. There was a non-significant trend towards reduced absolute bioavailability of theophylline from sustained-release formulations in smokers (percentage mean difference — 16% for one formulation and 13% for another). The trend was not observed for the plain uncoated tablet, which was rapidly absorbed (p〈0.01 to 0.05 in Ka, tmax and Cmax compared to sustained-release tablets). Similarity of the in vitro dissolution profiles of the two sustained-release formulations did not imply similarity of the in vivo absorption characteristics. Plasma clearances of theophylline and antipyrine were significantly correlated (p〈0.05,r=0.693,n=10). Thus, smoking enhanced the elimination of theophylline regardless of the dosage form administered. However, the extent to which habitual smoking may affect the hepatic first-pass effect on theophylline from sustained-release formulations requires further study. The results also suggest that theophylline and antipyrine may share a similar or common and presumably polycyclic hydrocarbon-inducible form(s) of microsomal drugmetabolizing enzyme.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00613931
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  • 3
    Electronic Resource
    Electronic Resource
    Pharmacokinetics and absolute bioavailability of carteolol, a new β-adrenergic receptor blocking agent (1983)
    Springer
    European journal of clinical pharmacology 25 (1983), S. 95-101 
    Details
    ISSN: 1432-1041
    Keywords: carteolol ; pharmacokinetics ; beta-adrenoreceptor blocking drug ; absolute bioavailability ; plasma levels ; urinary excretion ; renal handling
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics and absolute bioavailability of a new nonselective β-adrenoreceptor blocking agent, carteolol, were investigated after administration of single intravenous and oral doses to eight normal volunteers. Plasma and urine drug concentrations were measured by an HPLC method. The pharmacokinetic parameters after intravenous dosing were obtained by a two-compartment analysis: elimination or β-phase t1/2 4.7±0.3 h; Vc, 0.74±0.101/kg; Vd, 4.05±0.48 l/kg; Cl, 10.13±0.94 ml/min/kg; ClR, 6.56±0.58 ml/min/kg; and ClNR, 3.57±0.40 ml/min/kg. The absolute bioavailability obtained from plasma data was 83.7±8.0%, which was consistent with that derived from analysis of urine of 82.7±4.2%. The amounts excreted unchanged in urine up to 48 h after the intravenous and oral doses were 65.0±1.5% and 53.8±3.2% of the administered doses, respectively. The t1/2 for removal of the drug derived from plasma and urine findings after intravenous and oral dosing were similar, which indicates that the main route of elimination of carteolol is via the kidneys. As the ClR of carteolol exceeded the Cl of creatinine there may be renal tubular secretion of the drug.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00544023
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  • 4
    Electronic Resource
    Electronic Resource
    Pharmacokinetics of SUN 1165, a new antiarrhythmic agent, in renal dysfunction (1991)
    Springer
    European journal of clinical pharmacology 40 (1991), S. 411-414 
    Details
    ISSN: 1432-1041
    Keywords: SUN 1165 ; renal failure ; antiarrhythmic agent ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics of a new Class I antiarrhythmic agent, SUN 1165, has been studied in 32 patients with varying degrees of renal impairment following a single oral dose of 50 mg. The apparent volume of distribution at steady state was 1.48 1 · kg−1, the absorption rate constant was 2.2 h−1, and plasma protein binding was 26.8% in subjects with normal renal function. These variables were not altered with renal impairment. More than 60% of SUN 1165 given orally was excreted unchanged via the kidney, both by tubular secretion and glomerular filtration. The elimination rate constant, the apparent total body clearance and the apparent renal clearance were linearly correlated with the endogenous creatinine clearance. The half-time of elimination was 3.4 h in normal subjects and it was prolonged to 23.7 h in severe renal failure (creatinine clearance below 20 ml · min−1 · 1.48 m−2). Dosage adjustment of SUN 1165 is necessary in renal failure.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00265853
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  • 5
    Electronic Resource
    Electronic Resource
    Transfer of the mitochondrial rps10 gene to the nucleus in rice: acquisition of the 5′ untranslated region followed by gene duplication (2000)
    Springer
    Molecular genetics and genomics 263 (2000), S. 733-739 
    Details
    ISSN: 1617-4623
    Keywords: Key words Mitochondria ; Gene transfer ; Ribosomal protein S10 ; Rice ; 5′ Untranslated region (UTR)
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract Mitochondrial ribosomal protein S10 (rps10) is encoded by the mitochondrial genome in potato and pea. Here we show that the rps10 gene is absent from the mitochondrial genome of rice and has been transferred to the nucleus. Cloning and transcriptional analysis show that there are two rps10 genes in the rice nuclear genome and that their transcripts differ in abundance. Western analysis detected the RPS10 protein in the soluble fraction of rice mitochondria, although neither RPS10 has any obvious N-terminal presequence for targeting to mitochondria. This result suggests that targeting information is present in the internal region of rice RPS10. Genomic sequence analysis indicated that each rps10 gene has an intron in the 5′ untranslated region (5′ UTR) and that these intron sequences are homologous to each other. This result strongly suggests that a duplication event occurred after transfer of the rps10 gene to the nucleus. The duplicated rps10 genes have since been translocated to different chromosomes, because the two rps10 genes were mapped on chromosomes 6 and 12 by RFLP analysis. Interestingly, the 5′ UTR and the intron of the rice rps10 genes are homologous to sequences found in several rice genes with various functions, such as osk4, EF-1β2 and RAG1, suggesting a common origin and a functional role for the 5′ UTR. Acquisition of the 5′ flanking region might have accelerated the activation of the mitochondrial rps10 gene which was transferred to the nuclear genome.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s004380051222
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  • 6
    Electronic Resource
    Electronic Resource
    Sequence-tagged sites (STSs) as standard landmarkers in the rice genome (1994)
    Springer
    Theoretical and applied genetics 89 (1994), S. 728-734 
    Details
    ISSN: 1432-2242
    Keywords: STS ; RFLP ; Rice ; Genetic map ; Coding region
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract Generating sequence-tagged sites (STSs) is a prerequisite to convert a genetic map to a physical map. With the help of sequence information from these STSs one can also isolate specific genes. For these purposes, we have designed PCR primer sets, of 20 bases each, by reference to sequences of restriction fragment length polymorphism (RFLP) landmarkers consisting of rice genomic clones. These markers were evenly distributed over the 12 chromosomes and were shown to be single copy by Southern-blot analysis. With improved PCR protocols, 63 standard STS landmarkers in the rice genome were generated. Similarity searches of all partial sequences of RFLP landmarkers by the FASTA algorithm showed that 2 of the 63 RFLP landmarkers, G357 and G385, contained part of the ORFs of aspartate aminotransferase and protein kinase, respectively.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00223712
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  • 7
    Electronic Resource
    Electronic Resource
    Identification of a YAC clone carrying the Xa-1 allele, a bacterial blight resistance gene in rice (1996)
    Springer
    Theoretical and applied genetics 93 (1996), S. 117-122 
    Details
    ISSN: 1432-2242
    Keywords: Plant disease resistance ; Rice ; Xanthomonas oryzae pv. oryzae ; YAC
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract Map-based cloning methods have been applied for isolation of Xa-1, one of the bacterial blight resistance genes in rice.Xa-1 was previously mapped on chromosome 4 using molecular markers. For positional cloning of Xa-1, a high-resolution genetic map was made for theXa-1 region using an F2 population of 402 plants and additional molecular markers. Three restriction fragment length polymorphism (RFLP) markers, XNpb235, XNpb264 and C600 were found to be linked tightly to Xa-1, with no recombinants, and U08 750 was mapped 1.5 cM from Xa-1. The screening of a yeast artificial chromosome (YAC) library using theseXa-1-linked RFLP markers resulted in the identification of ten contiguous YAC clones. Among these, one YAC clone, designated Y5212, with an insert of 340 kb, hybridized with all three tightly linked markers. This YAC was confirmed to possess the Xa-1 allele by mapping the Xa-1 gene between both end clones of this YAC (Y5212R and Y5212L).
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00225736
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  • 8
    Electronic Resource
    Electronic Resource
    Identification of quantitative trait loci controlling heading date in rice using a high-density linkage map (1997)
    Springer
    Theoretical and applied genetics 95 (1997), S. 1025-1032 
    Details
    ISSN: 1432-2242
    Keywords: Key words RFLP markers ; Days-to-heading ; QTL analysis ; Rice ; Epistatic interaction
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract  Quantitative trait locus (QTL) analysis has been carried out to identify genes conferring heading date in rice. One hundred and eighty six F2 plants derived from a cross between a japonica variety, Nipponbare, and an indica variety, Kasalath, were used as a segregating population for QTL mapping and more than 850 markers were employed to identify QTLs. Scan-analysis revealed the existence of two QTLs with large effects, Hd-1 and Hd-2, one in the middle of chromosome 6 and one at the end of chromosome 7, respectively. For both loci, the Kasalath alleles reduced days-to-heading. In addition, three QTLs with minor effects, Hd-3, Hd-4 and Hd-5, were found to be located on chromosomes 6, 7 and 8 based on a secondary scan analysis which was carried out by removing the phenotypic effects of Hd-1 and Hd-2. For the three secondary loci, the Nipponbare alleles reduced days-to-heading. The five QTLs explained 84% of the total phenotypic variation in the F2 population based on a multiple-QTL model. The presence of a digenic interaction between Hd-1 and Hd-2 was clearly suggested.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s001220050658
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  • 9
    Electronic Resource
    Electronic Resource
    Genetic and physical mapping of xa13, a recessive bacterial blight resistance gene in rice (1999)
    Springer
    Theoretical and applied genetics 98 (1999), S. 1022-1028 
    Details
    ISSN: 1432-2242
    Keywords: Key words Genetic map ; Physical map ; Map-based gene cloning ; Disease resistance ; Rice ; DNA markers
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract  The recessive gene, xa13, confers resistance to Philippine race 6 (PXO99) of the bacterial blight pathogen Xanthomonas oryzae pv oryzae. Fine genetic mapping and physical mapping were conducted as initial steps in an effort to isolate the gene. Using nine selected DNA markers and two F2 populations of 132 and 230 plants, xa13 was fine-mapped to a genomic region 〈4 cM on the long arm of rice chromosome 8, flanked by two RFLP markers, RG136 and R2027. Four DNA markers, RG136, R2027, S14003, and G1149, in the target region were used to identify bacterial artificial chromosome (BAC) clones potentially harboring the xa13 locus from a rice BAC library. A total of 11 BACs were identified, forming four separate contigs including a single-clone contig, 29I3, associated with the RG136 STS marker, the S14003 contig consisting of four clones (44F8, 41O2, 12A16, and 12F20), the G1149 contig with two clones, 23D11 and 21H18, and the R2027 contig consisting of four overlapping clones, 42C23, 30B5, 6B7 and 21H14. Genetic mapping indicated that the xa13 locus was contained in the R2027 contig. Chromosomal walking on the R2027 contig resulted in two more clones, 33C7 and 14L3. DNA fingerprinting showed that the six clones of the R2027 contig were overlapping. Clone 44F8 hybridized with a single fragment from the clone 14L3, integrating the R2027 and S14003 contigs into a single contig consisting of ten BAC clones with a total size of approximately 330 kb. The physical presence of the xa13 locus in the contig was determined by mapping the ends of the BAC inserts generated by TAIL-PCR. In an F2 population of 230 plants, the BAC-end markers 42C23R and 6B7F flanked the xa13 locus. The probes 21H14F and 21H14R derived from BAC clone 21H14 were found to flank xa13 at a distance of 0.5 cM on either side, using a second F2 population of 132 plants. Thus, genetic mapping indicated that the contig and the 96-kb clone, 21H14, contained the xa13 locus.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s001220051163
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  • 10
    Electronic Resource
    Electronic Resource
    Detection of segregation distortions in an indica-japonica rice cross using a high-resolution molecular map (1996)
    Springer
    Theoretical and applied genetics 92 (1996), S. 145-150 
    Details
    ISSN: 1432-2242
    Keywords: Gametophyte gene ; Genetic map ; Hybrid sterility gene ; Rice ; Segregation distortion
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract We have constructed a high-resolution rice genetic map containing 1383 DNA markers covering 1575 cM on the 12 linkage groups of rice using 186 F2 progeny from a cross between a japonica variety, ‘Nipponbare’, and an indica variety, ‘Kasalath’. Using this high-resolution molecular linkage map, we detected segregation distortion in a single wide cross of rice. The frequencies of genotypes for 1181 markers with more than 176 genotype data were plotted along this map to detect segregation distortion. Several types of distorted segregation were observed on 6 of the chromosomes. We could detect 11 major segregation distortions at ten positions on chromosomes 1, 3, 6, 8, 9, and 10. The strongest segregation distortion was at 107.2 cM on chromosome 3 and may be the gametophyte gene 2 (ga-2). The ‘Kasalath’ genotype at this position was transmitted to the progeny with about a 95% probability through the pollen gamete. At least 8 out of the 11 segregation distortions detected here are new. The use of the high-resolution molecular linkage map for improving our understanding of the genetic nature and cause of these segregation distortions is discussed.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00223368
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