Library

X
feed icon rss

Your email was sent successfully. Check your inbox.

An error occurred while sending the email. Please try again.

Proceed reservation?

Export
  • 1
    Electronic Resource
    Electronic Resource
    Variability in the pharmacokinetics of epirubicin: a population analysis (1992)
    Springer
    Cancer chemotherapy and pharmacology 29 (1992), S. 391-395 
    Details
    ISSN: 1432-0843
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Population pharmacokinetic analysis of the anticancer agent epirubicin was carried out using the program NONMEM. Data were available from 36 patients aged 20–73 years, of whom 23 were women. All subjects exhibited normal liver and renal function. Epirubicin was given as a short-term i. v. infusion over the dose range of 25–100 mg/m2, and an average of 11 plasma samples/subject were taken for a period of up to 72 h after each dose. A Two compartment model was fitted to the data, characterised by the parameters clearance, volume of the central compartment, alpha and beta. Clearance was tested as a linear function of various demographic and/or biochemical features. A significant proportion of the variability in clearance could be attributed to sex, and also to age in women. For example, a 25-year-old man would display an average clearance of 95 l/h, whereas a 70-year-old woman would exhibit an average clerance of 64 l/h. Such differences in clearance might be important in the selection of epirubicin dose regimens.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00686009
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
    Paper (German National Licenses)
    Fulltext
  • 2
    Electronic Resource
    Electronic Resource
    The pharmacokinetics and pharmacodynamics of lignocaine and MEGX in healthy subjects (1987)
    Springer
    Journal of pharmacokinetics and pharmacodynamics 15 (1987), S. 101-115 
    Details
    ISSN: 1573-8744
    Keywords: Lignocaine ; MEGX ; pharmacokinetics ; pharmacodynamics ; active metabolite
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Lignocaine clearance declines during continuous intravenous infustion in man and in vitrostudies suggest that this may partly be due to inhibition by MEGX, a metabolite of lignocaine, MEGX is pharmacologically active in animals, but this is not yet proven in man. This study examined the pharmacokinetics and pharmacodynamics of lignocaine and MEGX in eight healthy male volunteers given lignocaine HCl 120mg, MEGX HCl 120 mg, lignocaine HCl 120 mg+MEGX HCl 120 mg, and placebo, administered according to a randomized double-blind protocol. One-, two-, or three-compartment models were fitted to drug and metabolite blood concentration-time profiles and clearance, volume (V ss ), andhalf-life values were calculated and compared by paired t-test. Systolic time intervals and QTinterval were recorded and compared by repeated measures ANOVA. When administered in combination with MEGX, lignocaine clearance was significantly reduced from 58±18 to 48±13 L hr(su−1) (p 〈0.02). The V(inss) was unchanged and there was a trend toward an increase in terminal half-life. Lignocaine, MEGX, and the combination significantly reduced QTinterval up to 30 min after injection and this was maintained to 2 hr with the lignocaine and the combination. Transient side effects were experienced with all active treatments, but were most pronounced with the combination. Thus, lignocaine clearance was inhibited by MEGX, which was pharmacologically active in man.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01062338
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
    Paper (German National Licenses)
    Fulltext
  • 3
    Electronic Resource
    Electronic Resource
    Pharmacokinetic and pharmacodynamic modelling of trimazosin and its major metabolite (1983)
    Springer
    Journal of pharmacokinetics and pharmacodynamics 11 (1983), S. 323-335 
    Details
    ISSN: 1573-8744
    Keywords: trimazosin ; metabolite ; pharmacokinetic model ; pharmacodynamic response
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract The pharmacokinetic and pharmacodynamic profiles of intravenous trimazosin, a postsynaptic α 1 antagonist, were analyzed empirically by integrated modelling techniques. The mean terminal elimination half-life for trimazosin was 186± 80 min and the mean elimination half-life of its alkyl hydroxylated metabolite (CP23445) was 93± 29 min. The placebo-corrected fall in systolic blood pressure after 5 min standing was most appropriately characterized in all subjects by a model that incorporated “effect” compartments for both parent drug and its metabolite.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01058953
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
    Paper (German National Licenses)
    Fulltext
  • 4
    Electronic Resource
    Electronic Resource
    Experimental design and efficient parameter estimation in population pharmacokinetics (1990)
    Springer
    Journal of pharmacokinetics and pharmacodynamics 18 (1990), S. 347-360 
    Details
    ISSN: 1573-8744
    Keywords: computer simulation ; parameter estimation ; population pharmacokinetics ; experimental design
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract A computer simulation technique used to evaluate the influence of several aspects of sampling designs on the efficiency of population pharmacokinetic parameter estimation is described. Although the simulations are restricted to the one-compartment one-exponential model, they provide the basis for a discussion of the structural aspects involved in designing a population study. These aspects include number of subjects required, number of samples per subject, and timing of these samples. Parameter estimates obtained from different sampling schedules based on two- and three-point designs are evaluated in terms of accuracy and precision. These simulated data sets include noise terms for both inter- and intraindividual variability. The results show that the population fixed-effect parameters (mean clearance and mean volume of distribution) for this simple pharmacokinetic model are efficiently estimated for most of the sampling schedules when two or three points are used, but the random-effect parameters (describing inter- and intraindividual variability) are inaccurate and imprecise for most of the sampling schedules when only two points are used. This drawback was remedied by increasing the number of data points per individual to three.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01062273
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
    Paper (German National Licenses)
    Fulltext
  • 5
    Electronic Resource
    Electronic Resource
    Analysis of animal pharmacokinetic data: Performance of the one point per animal design (1995)
    Springer
    Journal of pharmacokinetics and pharmacodynamics 23 (1995), S. 551-566 
    Details
    ISSN: 1573-8744
    Keywords: population pharmacokinetics ; preclinical ; parameter estimation ; sample size ; variability ; one sample per animal
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract A simulation study was carried out to determine the impact of various design factors on the accuracy and precision with which population pharmacokinetic parameters are estimated in preclinical pharmacokinetic studies. A drug given by intravenous bolus injection and having monoexponential disposition characteristics was assumed. The factors investigated were (i) number of animals sampled at specified times with one observation taken per animal, (ii) error in observed concentration measurements, and (iii) doubling the number of observations per animal while varying the number of animals. Data were analyzed with the NONMEM program, and the least number of animals per time point (where each animal supplied one concentration-time point) required for accurate and precise parameter estimation was determined. The one observation per animal design yielded biased and imprecise estimates of variability, and residual variability could not be estimated. Increasing the error in the concentration measurement led to a significant deterioration in the accuracy and precision with which variability was estimated. Obtaining a second sample from each animal practically eliminated bias and facilitated the partitioning of interanimal variability and residual intraanimal variability, by introducing information about the latter. Doubling the total number of observations per animal required using half (i.e., 50) the total number of animals required for accurate and precise parameter estimation with the one sample per animal design.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02353461
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
    Paper (German National Licenses)
    Fulltext
  • 6
    Electronic Resource
    Electronic Resource
    Effect of misspecification of the absorption process on subsequent parameter estimation in population analysis (1993)
    Springer
    Journal of pharmacokinetics and pharmacodynamics 21 (1993), S. 209-222 
    Details
    ISSN: 1573-8744
    Keywords: population pharmacokinetics ; NONMEM ; absorption ; experimental design
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract A prospective simulation study has been carried out to evaluate the effect of potential misspecification of the absorption rate constant (ka) in population pharmacokinetic analysis when few to no concentration-time data were available in the absorption phase and estimation of kawas not possible. Data were simulated for 100 subjects using a one-compartment model at steady state with first-order input. Data were generated over a range of kavalues: kawas misspecified in the NONMEM analysis by factors of 0.25, 0.5,1, 2, 3, and 4. In general, clearance (CL)was typically estimated with a small, constant underprediction, regardless of the range of misspecification of ka or whether data were present in the absorption phase. The same was not true for volume of distribution (V),values were biased and sensitive to the degree of misspecification, but only when the data contained even a little information about absorption. If studies are to be designed in which information absorption is either not required or is of no therapeutic use, then blood samples could be concentrated in the postabsorption phase and the absorption input fixed according to the best a priori information available.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01059771
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
    Paper (German National Licenses)
    Fulltext
  • 7
    Electronic Resource
    Electronic Resource
    Modeling of drug response in individual subjects (1980)
    Springer
    Journal of pharmacokinetics and pharmacodynamics 8 (1980), S. 115-130 
    Details
    ISSN: 1573-8744
    Keywords: disopyramide ; digoxin ; β-methyl digoxin ; pharmacokinetic model ; pharmacodynamic response ; individual response ; multiple linear regression
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Pharmacokinetic and drug response data from individual subjects are analyzed empirically by two different mathematical techniques. The drugs involved are the antiarrhythmic agent disopyramide, whose kinetics can be described by a two-compartment model, and two cardiac glycosides, digoxin and β-methyl digoxin, for which three-compartment models are appropriate. The first analytical approach uses multiple linear regression to describe response in terms of the amount of drug in several kinetic compartments. The second approach describes response in terms of the drug concentration in an “effect” compartment. Both approaches describe the data equally well and require the same number of parameters for model specification.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01065188
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
    Paper (German National Licenses)
    Fulltext
  • 8
    Electronic Resource
    Electronic Resource
    Experimental Design and Efficient Parameter Estimation in Preclinical Pharmacokinetic Studies (1995)
    Springer
    Pharmaceutical research 12 (1995), S. 729-737 
    Details
    ISSN: 1573-904X
    Keywords: population pharmacokinetics ; preclinical ; destructive (quantic) ; simulation ; experimental design ; parameter estimation ; design number ; confidence intervals coverage
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Monte Carlo simulation technique used to evaluate the effect of the arrangement of concentrations on the efficiency of estimation of population pharmacokinetic parameters in the preclinical setting is described. Although the simulations were restricted to the one compartment model with intravenous bolus input, they provide the basis of discussing some structural aspects involved in designing a destructive (“quantic”) preclinical population pharmacokinetic study with a fixed sample size as is usually the case in such studies. The efficiency of parameter estimation obtained with sampling strategies based on the three and four time point designs were evaluated in terms of the percent prediction error, design number, individual and joint confidence intervals coverage for parameter estimates approaches, and correlation analysis. The data sets contained random terms for both inter- and residual intra-animal variability. The results showed that the typical population parameter estimates for clearance and volume were efficiently (accurately and precisely) estimated for both designs, while interanimal variability (the only random effect parameter that could be estimated) was inefficiently (inaccurately and imprecisely) estimated with most sampling schedules of the two designs. The exact location of the third and fourth time point for the three and four time point designs, respectively, was not critical to the efficiency of overall estimation of all population parameters of the model. However, some individual population pharmacokinetic parameters were sensitive to the location of these times.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1016267811074
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
    Paper (German National Licenses)
    Fulltext
Close ⊗
This website uses cookies and the analysis tool Matomo. More information can be found here...