The effects of age and smoking on the plasma protein binding of lignocaine and diazepam.

Davis, Donald W.; Sh, Grossman; Kitchell, BB; Shand, David G.; Routledge, PA

doi:10.1111/j.1365-2125.1985.tb02641.x

Cited by 37 publications

(20 citation statements)

References 20 publications

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“…The lack of effect of sex on HSA confirms (Davis et al, 1985;Verbeeck et al, 1984;Wallace et al, 1976 Davis et al (1985). Light smoking (3-10 cigarettes per day) did not distort the effect of age on HSA concentration or the lack of effect of age on AAG concentration.…”

Section: Discussionmentioning

confidence: 92%

“…Although others have suggested that AAG concentrations increase with increasing age in healthy subjects, the effect of age in these studies was small (Abernathy et al, 1984;Davis et al, 1985;Verbeeck et al, 1984) with little or no clinical consequences, as it has been shown that the plasma binding of lignocaine and pethidine is correlated significantly with AAG concentrations, but not with age (Davis et al, 1985;Herman et al, 1985).…”

Section: Discussionmentioning

confidence: 96%

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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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Section: Discussionmentioning

confidence: 92%

Section: Discussionmentioning

confidence: 96%

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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“…In view of previous in vitro studies in normal volunteers (Routledge et al, 1980a) (Davies et al, 1985;Grossman et al, 1982;Routledge et al, 1980Routledge et al, a,b, 1981. Similarly the partial regression coefficient, B, appears to be similar in several disease states in which lignocaine binding varies markedly .…”

Section: Discussionmentioning

confidence: 99%

A free lignocaine index as a guide to unbound drug concentration.

Routledge¹,

Jd²,

Barchowsky³

et al. 1985

Brit J Clinical Pharma

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A free lignocaine index was developed on the basis of measurements of plasma lignocaine and its principle binding protein, alpha 1‐acid glycoprotein (AAG) in 80 samples from 16 patients admitted to the coronary care unit and given prophylactic lignocaine therapy. The free drug fraction, fu, of lignocaine was determined by equilibrium dialysis and its relationship to AAG and total lignocaine concentration (T) defined by multiple linear regression analysis as l/fu = 1.45 + 0.023 (AAG) ‐0.129 (T) (multiple r = 0.872, P less than 0.001). This relationship was used to calculate the 'free lignocaine index' as fu X T and compared with the observed value obtained by equilibrium dialysis of 178 samples from 41 separate subjects who received lignocaine after suspected myocardial infarction. There was a highly significant relationship (r = 0.933, n = 178, P less than 0.001) between the observed and predicted values. We conclude that the free drug index may be useful in rapidly assessing the unbound (free) concentration of lignocaine in plasma.

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“…There is a reduction in blood albumin concentration of about 10% in older people (Greenblatt, 1979;Campion et al, 1988) and possibly an increase in ␣1-acid glycoprotein (Verbeeck et al, 1984), probably secondary to age-associated inflammatory disease (Grandison and Boudinot, 2000). This decrease of albumin has been reported to be associated with an increase in the unbound fraction of many drugs including phenytoin (Patterson et al, 1982), diazepam (Davis et al, 1985), and piroxicam (Boudinot et al, 1993), but not of prazosin (Andros et al, 1996), warfarin (Shepherd et al, 1977), and verapamil (Schwartz et al, 1994). On average, the unbound fraction of drugs increases by approximately 10%, matching the age-related decrease in albumin (Grandison and Boudinot, 2000).…”

Section: B Volume Of Distribution and Agingmentioning

confidence: 99%