Pharmacokinetic Study of CPT-11, Raltegravir and Midazolam With Characterisation of UGT1A1 Genotype
To correlate pharmacokinetic parameters of raltegravir and midazolam with irinotecan
(CPT-11) and its metabolite SN-38.
To correlate the genotype of UGT1A1 of patients receiving CPT-11 chemotherapy with
irinotecan and raltegravir pharmacokinetic parameters.
To model pharmacokinetic and pharmacodynamic behaviour of CPT-11 in the study population.
VI. Abstract of Research Proposal In no more than 300 words, describe concisely the specific
aims, hypotheses, methodology and approach of the application, indicating where appropriate
the application's importance to science or medicine. The abstract must be self-contained so
that it can serve as a succinct and accurate description of the application when separated
from it. Please use lay terms. If this not possible, the technical and medical terms should
be explained in simple language. The pharmacokinetic parameters of raltegravir will
correlate well with irinotecan (CPT-11) and its metabolite SN-38 and better than midazolam.
Raltegravir pharmacokinetic parameters can be used to predict the genotype of UGT1A1 of
patients receiving CPT-11 chemotherapy with irinotecan. Patients who are prescribed the
CPT-11 containing regimen FOLFIRI will be selected for the study.
Subjects will then undergo the raltegravir and midazolam test one day before the first dose
of their chemotherapy. Pharmacokinetic sampling will occur for these 2 days. The raltegravir
and midazolam test will be carried out under fasting conditions (minimum 10 hours). Between
8 to 9 am, one mg of midazolam will be administered intravenously over 30 seconds. At the
same time, raltegravir 400 mg will be administered orally with water. Blood samples will be
drawn at specified times for pharmacokinetic analysis from a heparinised butterfly needle in
the opposite arm.
On the next day, FOLFIRI will be administered as follows:
CPT-11 at 180 mg/m2 in 250 mL Normal Saline over 90 min followed by Leucovorin at 400 mg/m2
in 250 mL Normal Saline over 2 hours followed by 5-Flourouracil 400 mg/m2 IV bolus followed
by 5-Flourouracil 2400 mg/m2 over 46 hours. Premedications may be administered as per
routine clinical practice. Blood will be taken at specified times for pharmacokinetic
analysis. The pharmacokinetic parameters of the raltegravir and midazolam will be compared
with the pharmacokinetic parameters of CPT-11 and its metabolite SN-38. Correlation analysis
will be performed on the parameters to find the raltegravir or midazolam parameters which
correlate best with the CPT-11 and SN-38 parameters. CPT-11 and raltegravir parameters will
be correlated with UGT1A1 and other demographic information.
Allocation: Non-Randomized, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Correlate pharmacokinetic parameters of raltegravir and midazolam with irinotecan (CPT-11) and its metabolite SN-38
Boon Cher Goh, MRCP
National University Hospital, Singapore
Singapore: Domain Specific Review Boards