Immunologisk aktivitet og biologiske legemidler påvirker legemiddelmetabolisme og -transport
Sammanfattning
Background
Cytokines are involved in the regulation
of expression and activity of CYP
enzymes and drug transporters (such as
P-glycoprotein). This article will focus on
the effect of immunological response and
treatment with therapeutic proteins on the
pharmacokinetics of substrates of CYP
enzymes or P-glycoprotein.
Methods
Relevant literature from PubMed searches
is reviewed.
Results
Disease-related immunological response
as well as therapeutic use of cytokines
reduces drug metabolism through CYP
enzymes. For most affected drugs, the
effect of the reduced metabolism leads to
an increased systemic exposure of about
50 %. Successful treatment of inflammatory
diseases with anti-cytokines may
increase the activity of CYP enzymes and
thus lead to therapeutic failure. The effect
of immunological stimuli on P-glycoprotein,
and consequently the pharmacokinetics
of substrates of P-glycoprotein,
varies in different tissues.
Conclusion
Treatment with therapeutic proteins
affects regulation of CYP enzymes, and
consequently the pharmacokinetics of
concurrently administered CYP substrates,
to an extent that may be considered
clinically relevant.