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I am working on a highly variable drugs (HVD), please post me if you
have any material, files related to HVD.
I am confused with Average BE and Scaled Average BE, Scaled BE.
Thank you very much for your time and consdieration.
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The following message was posted to: PharmPK
What do you wish to know about highly variable drugs? Are you
concerned about bioequivalrnce? Or are you concenred about how best to
manage therapy with a HVD? If it is the latter, then you might well
consider using the tools of nonparametric population modeling (which
estimates the entire joint model parameter distribution, not just
point estimators of an assumed normal or lognormal one) in combination
with multiple model dosage design, which uses the multiple support
points in the nonparametric PK/PD model to hit a desired therapeutic
target goal specifically with minimum expected weighted squared error
- maximum precision. You might also look at:
1. Bayard D, Jelliffe RW, Schumitzky A, Milman M, and Van Guilder
M: Precision Drug Dosage Regimens Using Multiple Model Adaptive
Control: Theory, and Application to Stimulated Vancomycin Therapy.
Vasudevan Memorial Volume on Theoretical Physics, Stochastic
Processes, and Biological Sciences. ed. by Rao KS and Sridhar R,
Allied Publishers Ltd., Madras, India, pp. 407-426, 1995.
2. Bustad A, Terziivanov D, Leary R, Port R, Schumitzky A, and
Jelliffe R: Parametric and Nonparametric Population Methods: Their
Comparative Performance in Analysing a Clinical Data Set and Two Monte
Carlo Simulation Studies. Clin. Pharmacokinet., 45: 365-383, 2006.
3. Jelliffe R: Goal-Oriented, Model-Based Drug Regimens: Setting
Individualized Goals for each Patient. Therap. Drug Monit. 22:
4. Jelliffe R, Bayard D, Milman M, Van Guilder M, and Schumitzky
A: Achieving Target Goals most Precisely using Nonparametric
Compartmental Models and "Multiple Model" Design of Dosage Regimens.
Therap. Drug Monit. 22: 346-353, 2000.
5. Jelliffe R, Schumitzky A, and Van Guilder M: Population
Pharmacokinetic / Pharmacodynamic Modeling: Parametric and
Nonparametric Methods. Therap. Drug Monit. 22: 354-365, 2000.
6. Bayard D, and Jelliffe R: A Bayesian Approach to Tracking
Patients having Changing Pharmacokinetic Parameters. J. Pharmacokin.
Pharmacodyn. 31 (1): 75-107, 2004.
7. Macdonald I, Staatz C, Jelliffe R, and Thomson A: Evaluation
and Comparison of Simple Multiple Model, Richer Data Multiple Model,
and Sequential Interacting Multiple Model (IMM) Bayesian Analyses of
Gentamicin and Vancomycin Data Collected From Patients Undergoing
Cardiothoracic Surgery. Ther. Drug Monit. 30:67-74, 2008.
You might also go to our web site www.lapk.org and click
aroound on NEW ADVANCES and TEACHING TOPICS for more information.
Very best regards,
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Please refer to USFDA Guidance regarding Average, Population and
Scaled BE isuues.
As for HVDs related issues in BE evaluation studies please refer to
USFDA and EMEA Guidances facing these problems.
Dimiter Terziivanov, MD,PhD,DSc, Professor and
Head, Clinic of Clinical Pharmacology and Pharmacokinetics,
Univ Hosp "St. Ivan Rilski",
15 Acad. Ivan Geshov st, 1431 Sofia, Bulgaria
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