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Файл:Ординатура / Хирургия / Библиотека им академика М.И. Перельмана / Книга_5320_Библиотеки_им_академика_М_И_Перельмана
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6
Complexation and Protein Binding
On completion of this chapter, the students should be able to
1.
2.
3.
biodistribution of drugs.
4.
6.1 Introduction
Figure 6.1
ions (substrate) (Figure 6.2
proteins in vivo
or the peripheral compartment), free drug concentration in plasma, and the duration of drug action. In add-
Figure 6.2) is ~97% bound to plasma
LEARNING OBJECTIVES
DOI: 10.1201/9781003389378-8
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Pharmaceutical Dosage Forms and Drug Delivery
FIGURE 6.1
FIGURE 6.2
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Complexation and Protein Binding
119
FIGURE 6.2 Continued
6.2 Types of Complexes
• Coordination complexes
A
+
()
()
33
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Pharmaceutical Dosage Forms and Drug Delivery
• Molecular complexes
6.2.1 Coordination Complexes
(a base) donates a pair of electrons (:) to the metal ion (an acid) to form the coordinate covalent bond.
+
gNHAgNH
+
2
:
→
2
+ 3
3)2]+ :, and Cl: donate a pair of
to
3)2]Cl.
2+
Figure 6.3).
FIGURE 6.3
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Complexation and Protein Binding
121
vitamin B12Figure 6.2), and heme is a coordin-
Figure 6.2
2+
)
state (Fe
3+
2+
Figure 6.2).
®), aurothioglucose (Solganol®), aurothiopropanol
®®Figure 6.2).
6.2.2 Molecular Complexes
6.2.2.1 Small Molecule– Small Molecule Complexes
•
of caffeine.
•
solution.
6.2.2.2 Small Molecule– Large Molecule Complexes
• in vitro
•
•
•
•
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FIGURE 6.4
Pharmaceutical Dosage Forms and Drug Delivery
FIGURE 6.5
•
Figure 6.4
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Complexation and Protein Binding
6.2.2.3 Large Molecule– Large Molecule Complexes
123
•
Figure 6.6
•
Figure 6.7).
6.3 Protein Binding
the substrate.
•
administration.
FIGURE 6.6
FIGURE 6.7
PL PL
d
k
k
k
]
k
]
k
θ
y
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Pharmaceutical Dosage Forms and Drug Delivery
•
•
6.3.1 Kinetics of Ligand– Protein Binding
+
a
(6.1)
ka and kd-
[PL]
=
a
=
d
(6.2)
[P][L
[P][L
(6.3)
[PL]
kd) has a unit of concentration (such as M
(ka
6.3.1.1 Parameters of Interest
=1 (6.4)
d
k
a
1. ka)
2.
protein, y
6.3.1.2 Experimental Setup
)
concentration, or vice versa. At each concentration, the amount of ligand bound is separated from the free
y
y
) as
=
y
max
n
+
d
[][]
L
Lk
Lk
[][]
][
[]
[]
[]
[]
[]
θ
[]
[]
d
[]
[]
y
[]
[]
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Complexation and Protein Binding
y represents the molar concentration, the amount of ligand bound per unit molar concentration,
or the amount of protein, and y
6.3.1.3 Determining ka and y
6.3.1.3.1 Nonlinear Regression I
max
centration of ligands bound to the protein per molar concentration of the protein. For the case of a single
[PL]
=
[P][PL]
(6.6)
kd,
PL
P
=
(6.7)
k
P
=
PP L
/
d
Lk
+
/
d
=
/
LkLk
+
d
=
/1
dd
(6.8)
+
For a single ligand- binding site per protein,
(6.9)
θ
=
(6.10)
+
k
θ
y
L
=
+
k
d
and kd as parameters.
(6.11)
L
Or,
yk=
max
L
d
(6.12)
+
L
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