Effect of Age on Protein Binding of Specific Drugs

1. Plasma Protein Binding of Drugs in
the Elderly
Presented by: Manju Jakhar
M.Pharm (Pharmacology)

2. Protein binding

3. Summary
 Binding to plasma proteins can affect the pharmacokinetics and pharmacodynamics of drugs.
 Age is one of many factors which can affect plasma protein binding of drugs.
 Unfortunately. very few generalities can be drawn from the studies of the effect of age
on protein binding. Whether age has an effect on protein binding is dependent not only
on the drug. but also on the manner in which the study is conducted.
 Several studies involve patients with various disease states making assessment of the effect of
age alone on protein binding difficult. Results of different studies on the same drug do not always
agree –in one case finding no change in protein binding with age and in another.
 Binding to plasma proteins is one of many factors affecting the pharmacokinetics and
pharmacodynamics of drugs.
 Since most drug responses are elicited at receptor sites in extravascular tissues, the
concentration of free or unbound drug in plasma is usually considered to be the active
concentration. Drug binding to plasma proteins can also affect the elimination of drugs from the
body (Rowland 1984).

4. Factors to be Considered in Evaluation
of Studies
1. Subjects
a) Number of Subjects
b) Age Range
c) Sex
d) Health
e) Drug Interactions
2 Protein Binding Methodology
a) Protein Binding Techniques
b) Temperature
c) Concentration of Drug
3 Statistical Analysis of Data
a) Data Presentation

5. Effect of Age on Protein Binding of
Specific Drugs
1. Disopyramide
 Most studies report no effect of age on plasma protein binding of disopyramide.
 Johnston and Hamer (1982) could not detect a correlation between the percentage bound
and age in 42 subjects ranging in age from 19 to 61 years.
 Bredesen and Kierulf (1984) could not detect a correlation between the binding of
disopyramide or its major metabolite and age in 60 patients (l6 to 89 years) with unspecified
disease states.
2. Lignocaine (Lidocaine)
 For lignocaine, the plasma protein binding increased with age (Davis et al. 1985).
 when the same data were examined by analysis of variance, the percentage free drug was
not significantly different between the 4 age groups in the study « 30 years, 30 to 49 years,
50 to 69 years and> 69 years).
 The binding ratio was correlated with plasma alpha1-acid glycoprotein concentration, but not
with levels of albumin or non-esterified fatty acids. Cusack et al. (1985) reported a significant
increase in the percentage bound and maximum binding capacity for lignocaine in plasma
from elderly patients, but no change in the dissociation constant for plasma protein binding
of the drug.

6. 3. Quinidine
 Protein binding of quinidine does not appear to be related to age.
 The percentage of free drug was not different in 8 elderly subjects (28.2% free,
ages 60 to 69 years) and 14 young subjects (24.6% free,ages 23 to 24 years) [Ochs
et al. 1978].
 In a second study, the percentage bound was not correlated with age in patients
receiving quinidine therapy (Y osselson-Superstine et al. 1982). However, in both
of these studies, protein binding was measured at variable concentrations of
quinidine in plasma. Ochs et a1. (1978) calculated the average percentage free for
each individual over a 30-hour period following administration of a single 180 to
300mg dose of quinidine.
 In the study of Yosselson-Superstine et al. (1982), binding was determined in
plasma samples collected in the morning from patients receiving 800 to 1400mg of
quinidine daily. Total plasma concentrations of quinidine ranged from 2.42 to
11.25 mg/L. Since protein binding of quinidine is concentration dependent, it
might be difficult to detect an effect of age on protein binding when samples from
each subject contain different concentrations of quinidine.

7. 4. Antibacterials
 Very few studies have investigated the effect of age on protein binding of
antibiotics. Drugs which have been studied include: ceftriaxone, penicillin,
sulphadiazine, vancomycin and the 2 constituents of co-trimoxazole
(trimethoprim and sulphamethoxazole)
 The percentage of free ceftriaxone in plasma was increased in elderly
subjects (15.7% free) compared with young subjects (13.6% free) [Luderer
et al. 1984]. The binding of penicillin was similar in subjects under and
over 50 years of age (Bender et al. 1975).
 The latter study, however, involved only 9 subjects, 5 younger than 50
years and 4 older than 50 years. Protein binding of sulphadiazine,
vancomycin, trimethoprim and sulphamethoxazole also remained
relatively constant in the elderly.