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  • 1
    Electronic Resource
    Electronic Resource
    Clinical pharmacokinetics of procainamide infusions in relation to acetylator phenotype (1979)
    Springer
    Journal of pharmacokinetics and pharmacodynamics 7 (1979), S. 69-85 
    Details
    ISSN: 1573-8744
    Keywords: procainamide ; pharmacokinetics ; constant-rate infusion ; acetylator phenotype ; pharmacogenetics ; renal impairment
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract The pharmacokinetics of procainamide was determined in 21 lidocaine-resistant patients who received the drug according to a pharmacokinetically designed double-infusion technique. Thirteen patients were phenotyped as slow acetylators, seven as fast, and one as intermediate. The total body clearances (ClT) of PA in slow and fast acetylators were 22.6 and 34.8 liters/hr, respectively. The fraction of PA cleared by the formation of NAPA in the corresponding acetylator group was 0.2 and 0.4. Renal impairment affected the pharmacokinetics of PA more profoundly as the ClTs of PA in patients with and without renal impairment were 17.9 and 31.2 liters/hr, respectively. None of the calculated volumes of distribution was affected by acetylator phenotype or renal impairment. These data identify the contribution of at least two of the major factors accounting for variability in PA disposition in patients undergoing therapy.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01059442
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  • 2
    Electronic Resource
    Electronic Resource
    Drug- or hormone-induced adaptation: Model of adrenergic hypersensitivity (1989)
    Springer
    Journal of pharmacokinetics and pharmacodynamics 17 (1989), S. 347-364 
    Details
    ISSN: 1573-8744
    Keywords: hypersensitivity ; propranolol ; pharmacokinetics ; pharmacodynamics ; modeling ; β receptor ; adrenergic stimulation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract A pharmacokinetic/pharmacodynamic model of hypersensitivity to adrenergic stimulation following abrupt withdrawal of chronic β blockade was developed. The model employs the Hill equation, a term which describes the competition between isoproterenol and l- propranolol for β receptors, and a kinetic term which characterizes the appearance and disappearance rates of up-regulated β receptors. The model predicted peak chronotropic hyperresponsiveness to isoproterenol 48 hr following abrupt withdrawal of chronic treatment with daily propranolol doses of 160 mg, and a drug half-life of 3.5 hr. The model also predicted that increasing the dose rate and prolonging the half-life of propranolol delayed and decreased the extent of adrenergic hypersensitivity. The time-course of adrenergic hypersensitivity simulated by our model was in excellent agreement with that observed in studies which were published earlier by our laboratory. The model underestimated the extent of adrenergic hypersensitivity. The results of our simulation are consistent with a β agonist-receptor-effector system, which involves spare receptors, amplification of response by second and third messengers, and β agonist-antagonist-induced receptor regulation.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01061901
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    Paper (German National Licenses)
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  • 3
    Electronic Resource
    Electronic Resource
    Influence of volume shifts on drug binding during equilibrium dialysis: Correction and attenuation (1983)
    Springer
    Journal of pharmacokinetics and pharmacodynamics 11 (1983), S. 483-498 
    Details
    ISSN: 1573-8744
    Keywords: volume-shift ; protein binding ; dextran ; disopyramide ; lidocaine ; propranolol ; diazepam ; clofibrate
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract A time-dependent volume shift from buffer to plasma, which occurs during equilibrium dialysis, decreased the protein binding of disopyramide and its capacity constant, and had no effect on the binding association constant. The volume-dependent decrease in disopyramidine binding may be corrected for by use of a derived equation. Inclusion of dextran, 2.5% (w/v), and use of a thick, low molecular weight cutoff membrane was the most effective technique in attenuating the volume shift. The plasma (serum) protein binding of the basic drugs lidocaine, disopyramide,propranolol, and diazepam was decreased when protein was diluted to 88 % or less of its undiluted concentration as a consequence of the volume shift. The protein binding of clofibrate, a highly bound acid drug, was more sensitive to volume shifts than the four basic drugs. Correction of drug binding for volume shifts was reasonably successful for most drugs. The highest binding measured for all drugs was associated with the lowest volume shift.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01062207
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  • 4
    Electronic Resource
    Electronic Resource
    Disopyramide pharmacokinetics and bioavailability following the simultaneous administration of disopyramide and14C-disopyramide (1984)
    Springer
    Journal of pharmacokinetics and pharmacodynamics 12 (1984), S. 289-313 
    Details
    ISSN: 1573-8744
    Keywords: protein binding ; pharmacokinetics ; bioavailability ; disopyramide ; heart failure
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract The pharmacokinetics and bioavailability of total (bound plus unbound) and unbound disopyramide were compared following the simultaneous administration of an oral dose of disopyramide and an intravenous dose of14C-disopyramide in five normal volunteers and in 11 patients with congestive heart failure. The binding of disopyramide varied between 60 and 92% in patients and between 81 and 88% in normal subjects at postequilibrium drug concentrations of 10−7M. The binding of disopyramide to serum protein was concentration-dependent in all study subjects at serum concentrations achieved following drug administration. The association constant for the first binding site in serum from normal subjects and patients averaged 8.7X105 M−1 and 4.4X10 5 M−1, respectively (p 〈 0.05). The unbound clearance of disopyramide averaged 277ml/min and 209 ml/min in normal subjects and in patients (p 〈 0.05). When normalized for body weight, the unbound clearance between patients and normal subjects was not significantly different. The elimination half-life of unbound concentrations in normal subjects and in patients averaged 4.9 and 6.1 h, respectively (p 〈 0.05). The clearance and elimination half-life of total disopyramide was the same in both groups. Although the bioavailability of disopyramide averaged 0.85 in both groups, it was more variable in patients owing to the variability in the fraction of the dose absorbed. The unbound renal clearance and volume of distribution at steady state of disopyramide was related to cardiac index. The ratio of elimination half-lives of total and unbound disopyramide was related to the extent of serum protein binding.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01061722
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  • 5
    Electronic Resource
    Electronic Resource
    Comparison of Single-Dose and Steady-State Nadolol Plasma Concentrations (1990)
    Springer
    Pharmaceutical research 7 (1990), S. 953-956 
    Details
    ISSN: 1573-904X
    Keywords: nadolol ; pharmacokinetics ; high-performance liquid chromatography (HPLC) ; nonlinearity ; β-blocker
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract The pharmacokinetics of nadolol have been previously reported to be linear between single and steady-state dosing. Data from a study in our laboratory suggested greater than expected β-blockade with nadolol at steady state. Because the early potency studies were single-dose studies, we hypothesized there was a nonlinearity in nadolol pharmacokinetics which produced higher than expected plasma concentrations at steady state. Six normal volunteers from the previous study (steady state) volunteered to participate in the single-dose study. Plasma concentrations were determined for 24 hr following a single dose of nadolol, 80 mg. A simple, inexpensive, and accurate method for determination of nadolol in plasma or serum by HPLC with fluorometric detection is described. The AUCo–tau at steady state was greater than the AUC0–∞ following a single dose in five of the six subjects. The mean ratio of AUCss/AUCsd was 2.54. This value would be unity in the presence of linear pharmacokinetics. We conclude that the principle of superposition is not applicable for nadolol.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1015954108734
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    Paper (German National Licenses)
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