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Pharmacokinetics and absolute bioavailability of lansoprazole (1996)

Gerloff, J. ; Mignot, A. ; Barth, H. ; [et al.]

Springer

European journal of clinical pharmacology 50 (1996), S. 293-297

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ISSN: 1432-1041

Keywords: Key words Lansoprazole; pharmacokinetics ; absolute bioavailability ; debrisoquine/sparteine phenotype ; mephenytoin phenotype

Source: Springer Online Journal Archives 1860-2000

Topics: Chemistry and Pharmacology , Medicine

Notes: Abstract Objective: In a crossover study 12 healthy volunteers received lansoprazole 15 mg or 30 mg orally, or 15 mg intravenously in randomized order as a single dose. Blood samples were taken and plasma levels of lansoprazole were determined using an HPLC method. The volunteers were phenotyped for the debrisoquine/sparteine and mephenytoin polymorphisms. Results: The total clearance was 517 ml⋅min−1, and the absolute bioavailability was 91% for the 30-mg and 81% for the 15-mg enteric-coated formulation. The elimination half-life was about 1 h. No correlation of the plasma levels to the sparteine metabolic ratio was found, and no correlation to the mephenytoin type could be established, since all volunteers of the mephenytoin type were extensive metabolizers. Although considerable variation, inter- and intraindividually, was observed, the increase in cmax and AUC did not deviate from dose proportionality. The present galenic formulation ensures a high bioavailability after a single dose.

Type of Medium: Electronic Resource

URL: http://dx.doi.org/10.1007/s002280050111

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Polymorphic CYP2D6 mediates O-demethylation of the opioid analgesic tramadol (1997)

Paar, W. D. ; Poche, S. ; Gerloff, J. ; [et al.]

Springer

European journal of clinical pharmacology 53 (1997), S. 235-239

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ISSN: 1432-1041

Keywords: Key words Tramadol ; CYP2D6

Source: Springer Online Journal Archives 1860-2000

Topics: Chemistry and Pharmacology , Medicine

Notes: Abstract Objective: This study was designed to investigate whether the in vivo metabolism of tramadol was influenced by CYP2D6 polymorphism. Methods: The extent of tramadol O- and N-demethylation was calculated by determining the amounts of tramadol and O- and N-desmethyltramadol in 24 h urine after ingestion of a test dose of tramadol. The O- and N-demethylation rates were calculated by dividing the 24-h urinary excretion amount of tramadol by that of O-and N-desmethyltramadol. Volunteers were phenotyped for CYP2D6 polymorphism using sparteine as an in vivo probe. Results and conclusion: High correlation was found between tramadol-O-demethylation and sparteine oxidation in 71 extensive metabolizers of sparteine (r s= 0.544). The mean metabolic ratio of tramadol O-demethylation was significantly higher in poor metabolizers of sparteine than in extensive metabolizers (4.4 vs 0.8). These in vivo results confirm that tramadol O-demethylation is carried out to a large extent by the polymorphic CYP2D6.

Type of Medium: Electronic Resource

URL: http://dx.doi.org/10.1007/s002280050368

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Choice of method for identifying germplasm with superior alleles (1988)

Gerloff, J. E. ; Smith, O. S.

Springer

Theoretical and applied genetics 76 (1988), S. 217-227

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ISSN: 1432-2242

Keywords: Exotic germplasm ; Computer simulation ; Testcross ; Upper bound ; Germplasm choice

Source: Springer Online Journal Archives 1860-2000

Topics: Biology

Notes: Summary An accurate and efficient method of screening the many germplasm sources available for their ability to improve elite, adapted germplasm is needed. The superiority measure (SX) of a population (P) was defined as the product of the frequency and relative superiority of the alleles in P that are more favorable than the best in an elite, adapted reference single cross I1×I2. A computer simulation was done to determine the correlations between various screening methods and the SX. The genetic model used included multiple alleles, no linkage, two types of non-epistatic gene action (additive and complete dominance) and two types of epistatic gene action (complementary and duplicate). Genetic variances in the populations and a statistic proposed by Dudley (SD={[P x I1-I1] [I1 xI2-I2]- [P x I2-I2]-[P x I2-I2] [I1 x I2-I1]}/{2[I1-I2]{) were inconsistently correlated with the SX over all types of gene action on the basis of rank correlations. The testcross to the single cross (TC[SC]=P x [I1 x I2]) and the upper bound on the SX (UBND=minimum [P x I1-I1, P x I2-I2]) were both consistently highly genetically correlated with the SX. In the set of populations simulated, there were positive correlations between products of allelic frequencies and effects at different classes of loci. The UBND usually had a higher rank correlation coefficient with the SX than did the TC(SC). The differences between their correlation coefficients were often insignificant. Although the TC(SC) gives no indication as to which inbred the population is more closely related, its ease of use and expected lowers standard error compared with the UBND indicate that it would be an appropriate choice of screening method for identifying superior populations in the sense defined.

Type of Medium: Electronic Resource

URL: http://dx.doi.org/10.1007/BF00257849

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Choice of method for identifying germplasm with superior alleles (1988)

Gerloff, J. E. ; Smith, O. S.

Springer

Theoretical and applied genetics 76 (1988), S. 209-216

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ISSN: 1432-2242

Keywords: Exotic germplasm ; Germplasm choice ; Testcross ; Upper bound

Source: Springer Online Journal Archives 1860-2000

Topics: Biology

Notes: Summary Elite, adapted germplasm is not likely to contain all the favorable alleles available in a species. Three statistics were evaluated for screening populations for their ability to contribute favorable dominant alleles not available in an elite single cross: (1) a statistic proposed by Dudley (SD)=[(P x I1-I1)(I1 x I2-I2)-(P x I2-I2) (I1 x I2-I1)]/[2(I1-I2)]; (2) the upper bound minimum (P x I1-I1, P x I2-I2) ; and (3) the testcross to the single cross [TC(SC)]=P x (I1 x I2), where P is the population to be evaluated and I1 and I2 are homozygous parents of the elite single cross I1×I2. A superiority measure for a population was defined as the product of frequencies of favorable alleles and effects summed over loci where I1×I2 is homozygous unfavorable. Of the statistics considered, TC (SC) should have the highest genetic correlation with the superiority measure under the assumptions made, require the fewest testing resources and have the smallest standard error. Methods considered for screening inbreds were: (1) SDI proposed by Dudley=[(I1 x IW)+(I2 x IW)-I1-I2-IW-(I1 x I2)]/4 ; (2) TC(SC)=IW x (I1 xI2); and (3) UBND=minimum where Iw is the inbred to be evaluated. The superiority measure of an inbred Iw was defined as the relative number of loci where I1 and I2 are unfavorable and Iw is favorable. The genetic correlation with the superiority measure should be highest for SDI. The larger number of measurements used in calculation, the necessity of evaluating potentially unadapted inbreds and larger testing resources required for SDI suggest further research should be done to evaluate these statistics.

Type of Medium: Electronic Resource

URL: http://dx.doi.org/10.1007/BF00257848

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