Personalised drug treatment better by design with PK/PD?
Sir,
The article by McDowell et al concludes that patients from different
ethnic groups have different risks for important ADRs based on a
metanalysis of adverse reactions due to drugs used in cardiovascular
medicine. Data are sparse and regulators should ask for better data before
licensing.
I would agree with the authors and suggest that the use of
Pharmacokinetic/Pharmacodynamic [PK/PD] modelling would greatly facilitate
this process. The European Commission sponsored a workshop to facilitate
the incorporation of PK/PD studies into drug development. Data presented
by Fuseau et al [1997] relating to naratriptan a serotonin agonist
treatment for acute migraine used a population approach and Bayesian
predictions to examine the PK/PD relationship for oral naratriptan during
phase II clinical trials. They reported that hepatic clearance of
naratriptan declined with age and hormone contraception use, potentially
increasing the likelihood of adverse events leading to product labelling
restrictions for elderly patients [Millson 2001]and with increased [50%]
peak plasma concentrations in female patients possibly leading to higher
efficacy in women. Whereas, in tobacco smokers and black patients the
hepatic clearance was increased leading to significantly lower exposure to
naratriptan.
This population PK/PD approach as exemplified with naratriptan should
be encouraged as a routine component of early human drug development,
which could predict the need for special precautions and potential
adverse events arising from differing circulating drug levels arising from
environmental factors (eg smoking), ageing and ethnicity.
David Millson MD MRCGP.
GP Principal & Visiting Professor of Medicines Management (Keele
University)
1.McDowell, SE, Coleman, JJ, Ferner, RE. Systematic review and meta-
analysis of ethnic differences in risks of adverse reactions to drugs used
in cardiovascular medicine.
BMJ 2006;332:1177-1180.
2.Fuseau, E, Kempsford, R, Winter, P et al. The integration of
population approach into drug development: a case
study,naratriptan.European Commission Conference, Geneva 1997:204-214: EUR
17611EN.
3.Millson, DS. The Clinical pharmacokinetics of the triptans: What
are the important clinical issues? 2001.Chapter8;57-71 International
Headache Research Seminars series Copenhagen, Edited Prof Pat
Humphrey.ISBN019 2632140
Competing interests:
None declared
Competing interests:
No competing interests
30 May 2006
David S Millson
GP Principal & Visiting Professor of Medicines Management (Keele University)
Leek Health Centre, Fountain Street, Leek ST13 6JB
Rapid Response:
Personalised drug treatment better by design with PK/PD?
Sir,
The article by McDowell et al concludes that patients from different
ethnic groups have different risks for important ADRs based on a
metanalysis of adverse reactions due to drugs used in cardiovascular
medicine. Data are sparse and regulators should ask for better data before
licensing.
I would agree with the authors and suggest that the use of
Pharmacokinetic/Pharmacodynamic [PK/PD] modelling would greatly facilitate
this process. The European Commission sponsored a workshop to facilitate
the incorporation of PK/PD studies into drug development. Data presented
by Fuseau et al [1997] relating to naratriptan a serotonin agonist
treatment for acute migraine used a population approach and Bayesian
predictions to examine the PK/PD relationship for oral naratriptan during
phase II clinical trials. They reported that hepatic clearance of
naratriptan declined with age and hormone contraception use, potentially
increasing the likelihood of adverse events leading to product labelling
restrictions for elderly patients [Millson 2001]and with increased [50%]
peak plasma concentrations in female patients possibly leading to higher
efficacy in women. Whereas, in tobacco smokers and black patients the
hepatic clearance was increased leading to significantly lower exposure to
naratriptan.
This population PK/PD approach as exemplified with naratriptan should
be encouraged as a routine component of early human drug development,
which could predict the need for special precautions and potential
adverse events arising from differing circulating drug levels arising from
environmental factors (eg smoking), ageing and ethnicity.
David Millson MD MRCGP.
GP Principal & Visiting Professor of Medicines Management (Keele
University)
1.McDowell, SE, Coleman, JJ, Ferner, RE. Systematic review and meta-
analysis of ethnic differences in risks of adverse reactions to drugs used
in cardiovascular medicine.
BMJ 2006;332:1177-1180.
2.Fuseau, E, Kempsford, R, Winter, P et al. The integration of
population approach into drug development: a case
study,naratriptan.European Commission Conference, Geneva 1997:204-214: EUR
17611EN.
3.Millson, DS. The Clinical pharmacokinetics of the triptans: What
are the important clinical issues? 2001.Chapter8;57-71 International
Headache Research Seminars series Copenhagen, Edited Prof Pat
Humphrey.ISBN019 2632140
Competing interests:
None declared
Competing interests: No competing interests