WELCOME TO

Course Title: Clinical Pharmacy-IV

Topic: Clinical Pharmacokinetics of
Cyclosporine

Ms. Anum Hanif

Lecturer
Faculty of Pharmacy
Hajvery University (HU)
 Learning Outcomes
Student will learn in this lecture about:
• Cyclosporine introduction
• Rationale for TDM
• Serum concentration response relationship
• Pharmacokinetic parameters
• Practical implications
• Clinical monitoring parameters
 Cycloporine

Chemical Nature:
• Neutral, lipophilic cyclic, endecapeptide extracted
from fungus tolypocladium inflatum gams.
• This is highly potent immunosuppressant drug, and
highly efficacious in reducing graft rejection.
Therapeutic Uses:
• It is principally used to reduce graft rejection after
organ and tissue transplantation.
• The drug has low therapeutic index.
Targeted Concentration:
100ng/daily - 200ng/ daily in the first six months after
transplantation and 80ng/ml-150ng/ml daily for 6 months
onwards.
Toxic Dose:
400ng/ml
• level below the lower limit of this window are associated
with an increased incidence of graft rejection.
• level above the upper limit are associated with an
increased incidence of nephrotoxicity and hypertoxicity.
Rational For TDM:
• Cyclosporin has low therapeutic index.
• It is effective against graft rejection and
• The nephrotoxic and hepatotoxic effects are
concentration related
Sampling Time:
• Sampling matrix should be whole blood.
• Samples should represent trough levels and be drawn
at steady state.
• Monitor every 2-3 days until patient is stable.
 Serum concentration response
relationship:
• It is very difficult to define therapeutic range,
since:
1. Measured concentration varies depending on
sampling matrix (i-e whole blood or plasma).
2. It depends upon whether the assay is specific for
cyclosporin alone or non specific to include
metabolites.
 Serum concentration response
relationship:
• Less than 200ng/ml ------ Target concentration
for postoperative phase of renal transplant.
• 200-400ng/ml -------- Target concentration for
postoperative phase of renal transplant.
• Greater than 400ng/ml ------ Toxicity.
 Pharmacokinetic Parameters:
•  
 Practical Implications:
• There is a wide interpatient variability in distribution
and elimination pharmacokinetic parameters,
absorption of standard formulation of cyclosporin is
variable and incomplete (F= 0.2- 0.5 in normal subject)
• In transplant patient this variation in bioavailability is
even greater and increased during the first few moths
after transplant.
• When using TDM with cyclosporin a no. of practical
points need to be considered.
 the sampling matrix should be the whole blood since there is a
variable distribution of cyclosporin between blood and plasma.
 sample should represent trough level and be drawn at steady
state which is achieved after 2-3 days, after initiating and
changing the dosage (average half life is 9-hrs).
 cyclosporin concentration monitoring should be undertaken
every 2-3 days in the immediate post operative phase until the
patient’s clinical condition is stable. Therefore monitoring can
be undertaken every 1-2 months
 TDM should be performed when changing brands of
cyclosporin since there is marked difference in the
bioavailability of different brands.
 Clinical monitoring parameters:
1.Observe bone marrow transplant pts for
symptoms of graft vs host disease (skin rash,
hyperbilirubinemia, raised ALT, AST etc)
2. Solid organ transplant recipients should be
observed for organ rejection.
3. Trough conc monitoring.
4. AUC monitoring.
Summary
The student have learnt about the:
• Cyclosporine introduction
• Rationale for TDM
• Serum concentration response relationship
• Pharmacokinetic parameters
• Practical implications
• Clinical monitoring parameters
1. Students you can ask any
question regarding this
lecture.
2. Google Classroom discussion
board.