Transcript clinical pharmacokinetics of lidocaine

CLINICAL
PHARMACOKINETICS
OF LIDOCAINE
Dr. Muslim Suardi
Faculty of Pharmacy
University of Andalas
2013
Lidocaine
• A local anesthetic agent that also has
antiarrhythmic effects
• Can also be considered for the treatment
of polymorphic ventricular tachycardia
THERAPEUTIC & TOXIC
CONCENTRATIONS
• When given iv-ly, the serum lidocaine
conc/time curve follows a 2 comp model
• The generally accepted therapeutic range
for lidocaine is 1.5–5 µg/mL.
• In the upper end of the therapeutic range
(>3 µg/mL), some patients will experience
minor side effects including drowsiness,
dizziness, paresthesias, or euphoria.
Continued
• Lidocaine Csr above the therapeutic range
can cause muscle twitching, confusion,
agitation, dysarthria, psychosis, seizures,
or coma.
• Cardiovascular adverse effects such as
atrioventricular block, hypotension, &
circulatory collapse have been reported at
lidocaine conc above 6 µg/mL, but are not
strongly correlated with specific serum
levels.
BASIC CLINICAL PK
PARAMETERS
• Lidocaine is almost completely eliminated
by hepatic metabolism (>95%).
• After im inj, absorption is rapid & complete
with max conc occurring about 1h after
administration & 100% BA as long as the
patient’s peripheral circulation is not
compromised due to hypotension or
shock.
• Plasma protein binding in normal
individuals is about 70%.
USE OF LIDO SERUM
CONCENTRATION TO ALTER
DOSE
Linear Pharmacokinetics Method
Problem
LK is a 50-year-old, 75-kg (5 ft 10 in)
male with ventricular tachycardia who
requires therapy with iv LIDO. He has
normal liver & cardiac function. The
current SS LIDO conc equals 2.2 µg/mL
at a dose of 2 mg/min.
Compute a LIDO dose that will provide
a Css of 4 µg/mL.
1. Compute New Dose to
Achieve Desired Csr
• The patient would be expected to achieve
SS conditions after 8h
• (5 t1/2 =5*1.5 h = 7.5 h) of therapy.
• Using linear PK, the new dose to attain the
desired conc should be proportional to the
old dose that produced the measured
conc:
• Dnew = (Css,new / Css,old)Dold = (4
µg/mL / 2.2 µg/mL) 2 mg/min = 3.6
mg/min, rounded to 3.5 mg/min
1.Continued
• The new suggested dose would be 3.5
mg/min of iv LIDO to be started
immediately.
• A SS LIDO Csr could be measured after
SS is attained in 3–5t1/2. Since the patient
is expected to have a t1/2 equal to 1.5h, the
LIDO Css could be obtained any time after
the first 8h of dosing (5 t1/2=5*1.5h = 7.5h)
1.Continued
• LIDO Csr should also be measured if the
patient experiences a return of their
ventricular arrhythmia, or if the patient
develops potential signs or symptoms of
LIDO toxicity.
INITIAL DOSAGE
DETERMINATION
METHOD
Literature Based Recommended Dosing
Problem
• LK is a 50yo, 75-kg (5 ft 10 in) male with
ventricular tachycardia who requires
therapy with iv LIDO. He has normal
liver & cardiac function. Suggest an
initial iv LIDO dosage regimen
designed to achieve a SS LIDO
concentration equal to 3µg/mL.
1. Choose LIDO Dose Based
on Disease States Present in
the patient
• A LIDO LD of 1–1.5 mg/kg & maintenance
infusion of 3–4 mg/min is suggested for a
patient without heart failure/liver disease
2. Compute Dosage Regimen
• Because the desired conc is in the lower
end of the therapeutic range, a dose in the
lower end of the suggested ranges will be
used.
• A LIDO LD of 1 mg/kg will be administered
• LD = 1 mg/kg*75 kg
=75 mg over 1.5–3min.
2. Continued
• A SS LIDO Csr could be measured after
SS is attained in 3–5t1/2. Since the patient
is expected to have a t1/2 equal to 1.5h, the
LIDO Css could be obtained any time after
the first 8h of dosing (5t1/2 = 5*1.5h= 7.5h).
LIDO Csr should also be measured if the
patient experiences a return of their
ventricular arrhythmia, or if the patient
develops potential signs of LIDO toxicity.
2. Continued
• A LIDO maintenance infusion equal to 3
mg/min would be administered after the
LD was given. An additional dose equal to
50% of the LD can be given if arrhythmias
recur 20–30 min after the initial LD.
USE OF LIDO BOOSTER DOSES
TO IMMEDIATELY INCREASE
Csr
Problems
• BN is a 57yo, 50-kg (5 ft 2 in) female
with ventricular tachycardia who is
receiving therapy with iv LIDO. She has
normal liver function & does not have
heart failure.
Problems
• After receiving an initial LD of LIDO (75
mg) & a maintenance infusion of LIDO
equal to 2 mg/min for 2h, her
arrhythmia reappears & a LIDO conc is
measured at 1.2 µg/mL.
• Compute a booster dose of LIDO to
achieve a LIDO conc equal to 4 µg/mL.
1. Estimate Vd According to Disease
States Present in the Patient
In the case of LIDO, the population
average central Vd equals 0.5 L/kg & this
will be used to estimate the parameter for
the patient.
The patient is nonobese, so her ABW will
be used in the computation:
V = 0.5 L/kg*50 kg
= 25 L.
2. Compute booster dose
• The booster dose is computed using the
following eq: BD = (Cdesired – Cactual)Vc
= (4 mg/L – 1.2 mg/L)25 L = 70 mg,
rounded to 75 mg of LIDO iv-ly over 1.5–3
min. If the MD was increased, it will take
an additional 3–5 estimated t1/2 for new
SS conditions to be achieved. LIDO Csr
could be measured at this time.
2. Continued
• LIDO Csr should also be measured if the
patient experiences a return of their
ventricular arrhythmia, or if the patient
develops potential signs of LIDO toxicity.