Diurnal Variation of α1-Acid Glycoprotein Concentration in Normal Volunteers

Yost, Richard L.; DeVane, C. Lindsay

doi:10.1002/jps.2600740718

Cited by 40 publications

(17 citation statements)

References 11 publications

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“…This suggestion is supported by the fact that the concentration of the protein in identical twins correlates very poorly (Storiko, 1968). Healthy subjects may have some variability in the concentration of AAG from day to day and even within the day (Yost & DeVane, 1985). However, large increases in AAG concentration can be related to intercurrent infection and sometimes to concomitant drug therapy.…”

Section: Antiarrhythmicsmentioning

confidence: 96%

The plasma protein binding of basic drugs.

Routledge¹

1986

Brit J Clinical Pharma

168

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The plasma protein binding of basic drugs appears to vary more than was at first assumed and is related to the marked intra‐and interindividual differences in one of the chief binding proteins, AAG. Changes in AAG concentrations will result in alterations in the distribution and metabolism of basic drugs which will complicate the interpretation of the relationship between total drug concentration and drug efficacy or toxicity. For some drugs, e.g. lignocaine, direct measurement of free concentrations may improve their clinical use but rapid and reliable techniques are as yet not readily available.

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Section: Antiarrhythmicsmentioning

confidence: 96%

The plasma protein binding of basic drugs.

Routledge¹

1986

Brit J Clinical Pharma

168

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“…The effect of age on AAG is not well established, possibly because of the large intrasubject variability in AAG levels (Paxton & Briant, 1983;Yost & De Vane, 1985). Some studies indicated a significant increase with age (Abernathy & Kerzner, 1984;Davis et al, 1985;Verbeeck et al, 1984).…”

Section: Introductionmentioning

confidence: 99%

“…Since AAG may be subject to diurnal variation (Yost & De Vane, 1985) samples were obtained at a fixed time (17.00 h) before dinner. Serum was obtained by centrifugation of clotted blood at 2800 g for 10 min and was separated immediately and stored at -20°C for subsequent analysis.…”

Section: Introductionmentioning

confidence: 99%

The effect of age on serum concentrations of albumin and alpha 1‐acid glycoprotein.

Veering

Burm

Souverijn

et al. 1990

Brit J Clinical Pharma

102

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1. Human serum albumin (HSA) concentrations and alpha 1‐acid glycoprotein (AAG) concentrations were measured in 68 subjects, 35 males and 33 females, aged 20‐90 years without evidence of acute or chronic inflammatory disease or malignancy. Subjects were drug free for at least 1 month. HSA and AAG concentrations were measured using rate nephelometry. 2. Age had no effect on alpha 1‐acid glycoprotein concentration, whereas plasma albumin levels decreased as a function of age in both sexes. We observed no differences between males and females in the plasma concentrations of HSA and AAG. 3. These data show that in healthy subjects the HSA concentration decreases with increasing age, whereas age, uncomplicated by disease does not influence AAG concentration.

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“…Some authors [18] have reported that AGP levels tend to rise in elderly humans and in Fischer 344 rats, although these changes are less marked than with albumin. Furthermore, AGP levels suffer important individual variations [19,20]. Other authors [21] found no changes in AGP levels depending on the age or a marked decrease in AGP plasma concentration with advancing age in pigs.…”

Section: Discussionmentioning

confidence: 99%

Age-Related Changes in Pharmacokinetics and Pharmacodynamics of Lerisetron in the Rat: A Population Pharmacokinetic Model

Jauregizar

Quintana²,

Súárez³

et al. 2003

Gerontology

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Background: The importance of studying the effects of age on the pharmacokinetics and pharmacodynamics of lerisetron – a new 5-hydroxytryptamine-3 (serotonin) receptor antagonist – comes from the facts that lerisetron will be administered to patients that are being treated with cytotoxic drugs and that the elderly frequently suffer from neoplastic diseases. Objective: The present study was designed to explore the effects of age on the pharmacokinetics and pharmacodynamics of lerisetron by using an aged rat model. A mixed-effects population study was carried out in order to analyze the sparse data and to create covariate models which could be used to derive dosage recommendations. Methods: Fischer 344 rats (n = 44) were divided into three groups, depending on their age: 5, 13, and 25 months. Blood samples were collected before administration of 200 µg/kg of lerisetron for measurements of albumin, α₁-acid glycoprotein, and unbound fraction of lerisetron. The lerisetron plasma concentrations were measured by high-performance liquid chromatography. A two-compartment model was fitted to the data using the nonlinear mixed-effects computer program WinNonMix. The population analysis was performed with the complete set of the collected data, and the potential sources of variability in the population parameters were investigated. Additionally, a pharmacodynamic study was performed. The effect of lerisetron (inhibition of the von Bezold-Jarisch reflex) was evaluated in young, adult, and senescent Fischer 344 rats. Results: The mean values of the individual Bayes estimates of the parameters showed a decrease in total clearance and distribution volume of the central compartment in old rats. The lerisetron free (unbound) fraction remained unchanged among the groups, and there were no significant differences in α₁-acid glycoprotein levels. The concentration-effect relationship was best described by a sigmoid E_max model. Since the drug concentration in plasma at half-maximal effect (EC₅₀) decreased in old rats, an increased sensitivity to the effect of lerisetron in old animals could be expected. Conclusion: Both pharmacokinetic changes (decreased volume of distribution and clearance and increased elimination half-life) and pharmacodynamic alterations (decrease in total and unbound EC₅₀) may be responsible for the different responses to lerisetron observed in old rats.

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Diurnal Variation of α1-Acid Glycoprotein Concentration in Normal Volunteers

Cited by 40 publications

References 11 publications

The plasma protein binding of basic drugs.

The plasma protein binding of basic drugs.

The effect of age on serum concentrations of albumin and alpha 1‐acid glycoprotein.

Age-Related Changes in Pharmacokinetics and Pharmacodynamics of Lerisetron in the Rat: A Population Pharmacokinetic Model

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