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  • 1
    Electronic Resource
    Electronic Resource
    Pharmacokinetics of ibuprofen in man—III: Plasma protein binding (1983)
    Springer
    Journal of pharmacokinetics and pharmacodynamics 11 (1983), S. 469-482 
    Details
    ISSN: 1573-8744
    Keywords: ibuprofen plasma protein binding ; bound/free ratio normally distributed ; free fraction not normally distributed ; binding capacity ; association constant
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Plasma protein binding of ibuprofen was measured by equilibrium dialysis on 406 plasma samples collected from 15 normal volunteers following doses of 400, 800, and 1200 mg of ibuprofen as tablets (N=102, 100, 104, respectively) and 420 mg as an aqueous solution (N=100). Individual subject bound concentration at dialysis equilibrium (Cbd) vs. free concentration at dialysis equilibrium (Cfd) were well fitted via computer to the Scatchard equation with one class of binding sites. The binding capacity averaged 1231 μM (range 848–1658 μM), and the association constant averaged 1.76 × 105M−1 (range 1.15 × 105 to 2.73 × 105M−1). Distributional analysis was performed on the free fraction (fd) and bound/free ratios (Cbd/Cfd=1/fd−1) at dialysis equilibrium for each treatment. Using pooled data of all four treatments, distributional analysis was also performed on the free fractions (f) and bound/free ratios (Cb/Cf=1/f−1) corresponding to the plasma drug concentrations in blood as it was withdrawn from the subjects. The bound/free ratios were normally distributed, whereas the distributions of the free fractions were skewed towards higher values.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01062206
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  • 2
    Electronic Resource
    Electronic Resource
    Pharmacokinetics of ibuprofen in man IV: Absorption and disposition (1984)
    Springer
    Journal of pharmacokinetics and pharmacodynamics 12 (1984), S. 381-399 
    Details
    ISSN: 1573-8744
    Keywords: ibuprofen ; absorption ; disposition ; multicompartmental model ; solution ; tablets ; absorption in multicompartment system without intravenous data
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Fifteen normal male volunters received 400, 800, and 1200 mg doses of ibuprofen as 1, 2, or 3 tablets, respectively, in crossover fashion, then 420 mg in solution form during the fourth week. Plasma concentration of ibuprofen was measured by an HPLC method. Individual subject concentration-time (C,t)data following the solution were analyzed by two different methods, and results unequivocally indicated the open two compartment model with first order absorption. However, the computer fitting of both arithmetic and geometric mean concentrations led to a different model. A method was developed to obtain absorption data (fraction of drug absorbed, Fa,versus time) for a multicompartmental system from oral data alone, without intravenous data. The method assumes that Vp is constant intrasubject and that absorption is complete following administration of both the solution and tablets. The method was successfully applied to the ibuprofen tablet data. It was shown also that such a method is necessary to obtain ibuprofen absorption data since intrasubject variation of the microscopic rate constants k12, ka21,and kel (as reflected by the intrasubject variation of the hybrid rate parameters λ1 and λ2 or Β and a) is of the same order of magnitude as intersubject variation. Absorption of ibuprofen from tablets was shown not to be simple first order as for the solution. The absorption profiles following one tablet were S- shaped, while those following 2 or 3 tablets had partial linear segments indicating zero order absorption.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01062664
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  • 3
    Electronic Resource
    Electronic Resource
    A nonlinear physiologic pharmacokinetic model: I. Steady-state (1985)
    Springer
    Journal of pharmacokinetics and pharmacodynamics 13 (1985), S. 73-92 
    Details
    ISSN: 1573-8744
    Keywords: pharmacokinetic theory ; venous equilibration (“well-stirred”) model ; compartment model ; linear pharmacokinetics ; nonlinear pharmacokinetics ; bioavailability ; intrinsic clearance ; liver blood flow ; clearance
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract The two-compartment model of Rowland et al.,(2) has been extended by replacing first order elimination with Michaelis-Menten elimination kinetics. All of the equations for steady-state concentrations and clearances for zero order (constant rate) input orally (into compartment #2) and intravenously (into compartment #1) are derived and reported. The steady-state concentration in compartment #1, following intravenous administration, is shown to be a nonlinear function of maximal velocity of metabolism, Vm,the Michaelis constant, Km,and liver blood flow, Q;and, following oral administration is dependent only upon Vm and Km and is independent of Q.However, oral bioavailability is a function of Vm, Km,and Q.The model allows physiologic pharmacokinetic interpretation of both linear and nonlinear data; and, together with simple modification of the model, can explain much observed pharmacokinetic data to date particularly for first-pass drugs. Future articles in the series will be concerned with single doses, evaluation of literature data in terms of the model, application of the theory in toxicology and in clinical pharmacokinetics and therapeutics.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01073657
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  • 4
    Electronic Resource
    Electronic Resource
    Gastrointestinal Transit of Nondisintegrating, Nonerodible Oral Dosage Forms in Pigs (1990)
    Springer
    Pharmaceutical research 7 (1990), S. 1163-1166 
    Details
    ISSN: 1573-904X
    Keywords: gastrointestinal transit ; animal model ; oral controlled release ; nondisintegrating ; plastic caplet ; Heidelberg capsule
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Gastrointestinal (GI) transit data necessary as “baseline” or “control” information were collected using pigs as animal models preliminary to bioavailability studies of new sustained action formulations. Density and size effects of nondisintegrating dosage forms on GI transit were investigated. Initially, enteric-coated nondisintegrating magnesium hydroxide caplets (density, 1.5 g/ml; size, 19.6 × 9.5 mm; weight, 1.2 g) were utilized in seven pigs. Prolonged gastric residence (〉5 days) occurred in every case for this dosage form. Therefore, nondisintegrating caplets of three densities (1.25, 1.45, and 2.3 g/ml) and three different sizes (large, 20 × 10 mm; medium, 10 × 10 mm; small, 5 × 10 mm) were studied in two more pigs. Roentgenography was used to visualize passage of caplets through the GI tract. Heidelberg pH capsules (size, 8 × 20 mm; density, 1.61 g/ml) were also used in this study. Total GI transit times range from 2 to 33 days for 22 administrations of these nondisintegrating dosage forms. Pigs are found to not be an appropriate model for evaluating bioavailability of nondisintegrating controlled-release dosage forms because total GI transit time (especially gastric transit) is much too long.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1015936426906
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  • 5
    Electronic Resource
    Electronic Resource
    Correlation of Ibuprofen Bioavailability with Gastrointestinal Transit by Scintigraphic Monitoring of 171Er-Labeled Sustained-Release Tablets (1987)
    Springer
    Pharmaceutical research 4 (1987), S. 486-489 
    Details
    ISSN: 1573-904X
    Keywords: scintigraphy ; neutron activation ; bioavailability ; ibuprofen ; sustained release ; gastrointestinal transit
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract External gamma scintigraphy was used to monitor the gastrointestinal (GI) transit of radiolabeled sustained-release tablets containing 800 mg ibuprofen in eight fasted healthy volunteers. Ibuprofen serum concentrations were determined from blood samples drawn sequentially over a 24-hr period. Serum concentrations and related parameters were correlated to the position of the dosage form in the GI tract from the scintiphotos. The sustained-release tablets were radiolabeled intact utilizing a neutron activation procedure, by incorporating 0.18% of 170Er2O3 (enriched to 〉96% 170Er) into the bulk formulation. After manufacture of the final dosage forms, the tablets were irradiated in a neutron flux (4.4 × 1013 n/cm2 · sec) for 2 min, converting the stable 170Er to radioactive 171Er (t 1/2 = 7.5 hr). Each tablet contained 50 µCi of 171Er at the time of administration. The scintigraphy studies suggested that the greatest proportion of ibuprofen was absorbed from this dosage form while the tablet was in the large bowel. The dosage forms eroded slowly in the small bowel and appeared to lose their integrity in the large bowel. In vitro studies showed only minimal effects of the neutron irradiation procedure on the dosage form performance.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1016475421474
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  • 6
    Electronic Resource
    Electronic Resource
    Absorption of Flurbiprofen in the Fed and Fasted States (1992)
    Springer
    Pharmaceutical research 9 (1992), S. 901-907 
    Details
    ISSN: 1573-904X
    Keywords: flurbiprofen ; oral absorption ; fasted state ; fed state ; gastric emptying
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract The oral absorption of flurbiprofen, an antiinflammatory nonsteroidal compound, was compared in the fasted vs the fed state. When ingested as an aqueous solution of the sodium salt, absorption kinetics followed a monoexponential pattern in half of the subjects and a bimodal pattern with a lag time before the onset of the second phase of absorption in the other half of the subjects. When ingested in the free acid form as a tablet either with water (fasted state) or with water 15 min after 330 ml of apple juice (fed state), flurbiprofen absorption was always bimodal, and the lag time before the onset of the second phase was shown to be dependent on the gastric emptying time (r = 0.623, P 〈 0.01). The gastric emptying times were significantly longer when the drug was administered in the fed state (average GET = 57 min in the fasted state and 102 min in the fed state; P 〈 0.01). These results suggest that gastric emptying effects are one important way in which absorption of drugs can be affected by meal intake.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1015800932454
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