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I am a novice in the design of population PK studies. I wish to carry out a study on the
impact on genetic polymorphisms of CYP2B6 and other covariates on the clearance of
nevirapine and efavirenz in a cohort of HIV/AIDS patients. The steady state plasma levels
will be determined. On carrying out a literature search I found that few similiar studies
took random blood samples at steady state. I hypothesize that patients who are homozygous
for the allelle that codes for poor metabosim have a clearance that is 30 % less than
normal. The prevalance of the homozygous trait is estimated at 10%. I intend to take at
least one blood sample patient and a second sample from at least a third of those who
agree to give a second sample. KIndly advise me on how to calculate the ideal sample size
and the sampling times. The study will be done on a Kenyan cohort.
Thank you
Faith A OKalebo
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Dear Faith,
The following work might be of help and can answer some of the questions you have posted:
Terziivanov, D. et al. Nonparametric Expectation Maximisation (NPEM) Population
Pharmacokinetic Analysis of Caffeine Disposition from Sparse Data in Adult Caucasians
Systemic Caffeine Clearance as a Biomarker for Cytochrome P450 1A2 Activity. Clin
Pharmacokinet 2003; 42 (15): 1393-1409.
As far as I know, for safety reasons, it is not recommended to send attachments via this
forum. For your convenience I can send you the paper as PDF file in case you are
interested in.
Greetings,
Dimiter T.
Dimiter Terziivanov, MD,PhD,DSc, Professor
Dept. of Pharmacology and Clinical Pharmacology
SOFIA UNIVERSITY
"ST. KLIMENT OHRIDSKI"
FACULTY OF MEDICINE
UNIV HOSP "LOZENETZ"
1 Koziak str.
1407 Sofia, BULGARIA
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The following message was posted to: PharmPK
Dear Faith -
1. It is not clear what the intended utility of the study is as the PK of the two drugs
are extensively studied. There is no reason to expect the effect of polymorphism would be
different in different regions of the world. You may want to think thr what exactly you
would benefit from this study.
2. Let us assume you are convinced this study is needed - the goal of such clinical
pharmacology studies is to characterize the PK and identify obvious differences between
groups. Hence the goal ought to be to estimate the mean PK parameters (say) with
reasonable precision. A SEM of 20% is reasonable. So you should use the known PK
characteristics of the two drugs and simulate your clinical trial under different
scenarios (various sample sizes and sampling schemes) and select the design which renders
you the target precision of the mean PK parameters.
Joga Gobburu, PhD, FCP, MBA | Professor | Executive Director
Center for Translational Medicine | School of Pharmacy | School of Medicine
N407, 20 N Pine, Baltimore, MD-21201
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