KELAS C

NAMA ANGGOTA KELOMPOK

1.
2.
3.
4.
5.

Armeili Puspita Dewi

(11 01 01 102)
Asih Kurniasari
(11 01 01 103)
Ayu Permata J.B
(11 01 01 104)
Denada Putri Syabrina (11 01 01 105)
Dewi Azzahra
(11 01 01 106)

Chlinical Pharmacokinetics
on Renal Failure Patients

Introduction
Chronic kidney disease is a common, progressive

illness that is becoming a global public health

problem.
In patients with kidney dysfunction, the renal
excretion of parent drug and/or its metabolites
will be impaired, leading to their excessive
accumulation in the body. In addition, the plasma
protein binding of drugs may be significantly
reduced, which in turn could influence the
pharmacokinetic processes of distribution and
elimination.
(Roger K. Verbeeck, 2009: 2)

Three major process of Elimination

in Kidney
1. Glomerulus filtration
2. Active tubulus

secretion
3. Active tubulus
reabsorption

Renal clearance
Renal clearance is the volume of blood or

plasma which is completely of the unchanged

drug by the kidney per unit time.
CLR =
Renal clearance is the ratio of sum of

glomerular filtration and secretion minus rate

of reabsorption to plasma drug concentration
(c).
CLR =
(Samudrala Vijay, 2011:8)

If renal clearance exceeds drug filtration rate,

there is net renal tubular secretion of the drug.

If renal clearance is less than drug filtration rate,
there is net renal tubular reabsorption of the
drug.

(Atkinson, 1999: 5)

Creatinine clearance
ClCl =

Normal value: 100-125 ml/min for 1.73m2

body surface area

Moderate renal failure: 20-50 ml/min
Severe renal failure: less than 10 ml/min

(Samudrala Vijay, 2011:10)

Renal impairment
The kidney is an important organ in regulating

body fluids, removal of metabolic waste,

electrolyte balance and drug excretion from
the body.
Impairment or degeneration of kidney
function affects the pharmacokinetics of the
drugs.
Some of the common causes for kidney failure
include disease, injury, and drug intoxication.

Effect of Renal Disease on

Pharmacokinetics
Pharmacokinetic processes such as drug

distribution (including volume of distribution and

renal excretion) altered by renal impairment.
Therapeutic and toxic respones may altered as a
result of changes in drug sensitivity at the
receptor site.
The effect of renal disease on pharmacokinetic
processes such as absorption, distribution,
metabolism, elimination is as follows.
Acute diseases or trauma to the kidney can
cause uremia, in which glomerular filtration is
impaired ore reduced, leading to accumulation of
excessive fluid and blood nitrogenous products

Effect of renal disease on drug

absorption
Impaired renal function will result in increased

bioavailability of drugs exhibiting first-pass

metabolism when the function of drug
metabolizing enzymes is compromised.

(Roger K.Verbeeck, 2009:5)

Effect of renal disease on drug

distribution
Impaired renal function is associated with important

changes in the binding of drugs to plasma proteins.

Protein binding in serum from uremic patients is
decreased.
Most acidic drugs bind to the bilirubin site on
albumin.
The reduced binding occurs when renal function is
impaired for the following reasons.
Reduction in serum albumin concentration
b. Structural changes in binding sites
c. Displacement of drug from albumin binding sites by
organic molecules that accumulate in uremia.
a.

The volume of distribution of a drug can

decrease if compounds normally excreted by

the kidney accumulate to the extent that
displacement of drug from tissue binding sites
occurs.
The decrease of albumin will increase the
volume of distribution.

(Samudrala Vijay, 2011:26)

Effect of renal disease on drug

elimination
The effect of renal disease on the elimination

of a drug depends on the renal status of the

patient and the elimination characteristics of
the drug.
For many drugs CLE consists of renal (CLR)
and non renal (CLNR) components.

CLE = CLR +
CLNR
Non renal excretion includes Biliary excretion,

Pulmonary excretion, salivery excretion, etc.

The total clearance (CLE) and the dose of

drug can influence the consentration of

steady-state (Css) in the blood.
The decrease of total clearance value will
increase the concentration of steady-state
(Css) in the blood.
Dose adjustments may be done by:
Reducing the drug dose
Lengthening the dosing interval

(Atkinson, 1999:4)

Effect of renal disease on drug

metabolism
Most drugs are not excreted by the kidneys

unchanged but are biotransformed to

metabolites that are then excreted.
Renal failure retard the excretion of metabolites.
Renal failure alteres the metabolic of clearance
of the drug.
The impact of impaired renal function on drug
metabolism is dependent on the metabolic
pathway.

(Atkinson, 1999:5)

Monitoring Patients Renal Function

1. Patients clinical condition
2. Biochemical data
3. Other biochemical abnormalities

Classification of Renal Failure

Classification

GFR (ml/min/1.73m2)

Serum Creatinine
(mol/L)

Mild

20 to 50

150 to 300

Moderate

10 to 20

300 to 700

< 10

> 700

Severe

Dosing in renal impairment

Predicting GFR using serum and urine

creatinine concentrations
Cockroft and Gault Equation
GFR =
F = 1.23 for males ans 1.04 for females

Examples estimating renal function

using serum creatinine
Patient details
Mr JB 75 years old gentleman admitted to the renal
unit.
Ideal body weight = 80 kg, serum creatinine = 400
mol/L
Urine creatinine = 3.7 mmol/L, 24 hr urine volume =
Classification
GFR
Serum creatinine
2400mls
(mls/min/1.73m2)
(mol/L)
Mild
Moderat
Moderate
e
Severe

20 to 50
10 to
10 to 20
20

150 to 300
to
300300
to 700
700

< 10

> 700

GFR =
=
= 16 ml/min = Moderate renal impairment

Dose adjustment in renal disease

In the renal disease, the renal clearance and

elimination rate are reduced, the elimination halflife is increased and the volume of distribution is
altered.
The half-lives of some drugs are changed
sufficiently in patients with impaired renal
function to warrant change in the usual dosage
regimen to prevent accumulation of the drug in
the body to toxic levels.
Generally, one should consider a possible,
modest decrease in drug doses when creatinine
is < 50-60mL/min

A moderate decrease in drug dose when

creatinine clearance is < 25-30 mL/min.

A substantial decrease in drug doses when
creatinine clearance is < 15 mL/min.

Approaches for dose adjustment

Decrease the drug dose and retain the usual

dosage interval.
Retain the usual dose and increase the
dosage interval.
Decrease the dosage and prolong the dosage
interval.
The dosage change is usually proportional to
the relative difference in half-life between the
patients with renal disease and the person
with normal renal function.

Patients with renal failure sometimes need

loading doses because the time required

reach steady state with a particular drug may
be much longer than in patients with normal
function. This is particularly important when
planning antibiotic or cardiac glycoside
theraphy.
When dosing interval extension is applied in
severe renal disease to drugs with short halflives, like the aminoglycoside antibiotics,
prolonged the periods of serum
concentrations below the therapeutic range
may result.

(Samudrala Vijay, 2011:30-33)

References
Verbeeck, R.K. 2009. Pharmacokinetics and Dosage

Adjustment in Patients with Renal Dysfunction.

Springer: Verlag
Vijay, Samudrala. 2011. Altered Pharmacokinetics

In Renal Insuffiency. Warangal: Departement of

Pharmaceutics Balaji Institute of Pharmaceutical
Sciences
Atkinson. 1999. Effect of Renal Disease on

Pharmacokinetics

Thank you