A Comprehensive Review of the Clinical Pharmacokinetics, Pharmacodynamics, and Drug Interactions of Nirmatrelvir/Ritonavir
Clinical Pharmacokinetics,
Journal Year:
2024,
Volume and Issue:
63(1), P. 27 - 42
Published: Jan. 1, 2024
Nirmatrelvir
is
a
potent
and
selective
inhibitor
of
the
severe
acute
respiratory
syndrome
coronavirus
2
(SARS-CoV-2)
main
protease
that
used
as
an
oral
antiviral
disease
2019
(COVID-19)
treatment.
To
sustain
unbound
systemic
trough
concentrations
above
in
vitro
90%
effective
concentration
value
(EC90),
nirmatrelvir
coadministered
with
100
mg
ritonavir,
pharmacokinetic
enhancer.
Ritonavir
inhibits
nirmatrelvir's
cytochrome
P450
(CYP)
3A4-mediated
metabolism
which
results
renal
elimination
becoming
primary
route
when
dosed
concomitantly.
exhibits
absorption-limited
nonlinear
pharmacokinetics.
When
ritonavir
patients
mild-to-moderate
COVID-19,
reaches
maximum
3.43
µg/mL
(11.7×
EC90)
approximately
3
h
on
day
5
dosing,
geometric
mean
1.57
(5.4×
EC90).
Drug
interactions
nirmatrelvir/ritonavir
(PAXLOVIDTM)
are
primarily
attributed
to
ritonavir-mediated
CYP3A4
inhibition,
lesser
extent
CYP2D6
P-glycoprotein
inhibition.
Population
pharmacokinetics
quantitative
systems
pharmacology
modeling
support
twice
daily
dosing
300
mg/100
for
days,
reduced
150
dose
moderate
impairment.
Rapid
clinical
development
response
emerging
COVID-19
pandemic
was
enabled
by
innovations
research,
including
adaptive
phase
1
trial
design
allowing
direct
pivotal
development,
fluorine
nuclear
magnetic
resonance
spectroscopy
delineate
absorption,
distribution,
metabolism,
excretion
profiles,
innovative
applications
model-informed
drug
accelerate
development.
Language: Английский
Real-World Evidence of the Top 100 Prescribed Drugs in the USA and Their Potential for Drug Interactions with Nirmatrelvir; Ritonavir
Jacqueline Gerhart,
No information about this author
Florin Draica,
No information about this author
Michael Benigno
No information about this author
et al.
The AAPS Journal,
Journal Year:
2023,
Volume and Issue:
25(5)
Published: July 20, 2023
Nirmatrelvir
(coadministered
with
ritonavir
as
PAXLOVIDTM)
reduces
the
risk
of
COVID-19-related
hospitalizations
and
all-cause
death
in
individuals
mild-to-moderate
COVID-19
at
high
progression
to
severe
disease.
Ritonavir
is
coadministered
a
pharmacokinetic
enhancer.
However,
may
cause
drug-drug
interactions
(DDIs)
due
its
various
drug-metabolizing
enzymes
transporters,
including
cytochrome
P450
(CYP)
3A,
CYP2D6,
P-glycoprotein
transporters.
To
better
understand
extent
DDIs
(or
lack
thereof)
nirmatrelvir;
clinical
setting,
this
study
used
real-world
evidence
(RWE)
from
Optum
Clinformatics
Data
Mart
database
identify
top
100
drugs
most
commonly
prescribed
US
patients
The
were
identified
based
on
total
counts
associated
high-risk
(i.e.,
≥
1
medical
condition
an
increased
COVID-19)
who
continuously
enrolled
throughout
2019
had
prescription
claim.
Each
was
then
assessed
for
DDI
their
metabolism,
excretion,
transport
pathways
available
prescribing
literature
sources.
Seventy
not
expected
have
ritonavir,
many
cardiovascular
agents,
anti-infectives,
antidiabetic
antidepressants.
Conversely,
30
drugs,
corticosteroids,
narcotic
analgesics,
anticoagulants,
statins,
sedatives/hypnotics,
ritonavir.
This
RWE
analysis
complementary
information
other
management
tools
guiding
healthcare
providers
managing
DDIs.
Language: Английский
Epithelial-mesenchymal transition in cancer: A focus on itraconazole, a hedgehog inhibitor
Biochimica et Biophysica Acta (BBA) - Reviews on Cancer,
Journal Year:
2025,
Volume and Issue:
unknown, P. 189279 - 189279
Published: Feb. 1, 2025
Cancer,
and
the
resulting
mortality
from
it,
is
an
ever-increasing
concern
in
global
health.
Cancer
stems
metastatic
progression
of
disease,
by
dissemination
tumor
cells.
Epithelial-Mesenchymal
Transition,
major
hypothesis
purported
to
be
origin
metastasis,
confers
mesenchymal
phenotype
epithelial
cells
a
variety
contexts,
physiological
pathological.
EMT
cancer
leads
rise
cancer-stem-like
cells,
drug
resistance,
relapse,
malignancy.
Inhibition
could
potentially
attenuate
mortality.
While
novel
molecules
for
inhibiting
are
underway,
repurposing
drugs
also
being
considered
as
viable
strategy.
In
this
review,
Itraconazole
focused
upon,
repurposed
molecule
mitigate
EMT.
known
inhibit
Hedgehog
signaling,
light
shed
upon
existing
evidence,
well
questions
remaining
answered.
Language: Английский
Drug–Drug Interactions Involving Dexamethasone in Clinical Practice: Myth or Reality?
Venceslas Bourdin,
No information about this author
W. Bigot,
No information about this author
Anthony Vanjak
No information about this author
et al.
Journal of Clinical Medicine,
Journal Year:
2023,
Volume and Issue:
12(22), P. 7120 - 7120
Published: Nov. 15, 2023
Concomitant
administration
of
multiple
drugs
frequently
causes
severe
pharmacokinetic
or
pharmacodynamic
drug–drug
interactions
(DDIs)
resulting
in
the
possibility
enhanced
toxicity
and/or
treatment
failure.
The
activity
cytochrome
P450
(CYP)
3A4
and
P-glycoprotein
(P-gp),
a
drug
efflux
pump
sharing
localization
substrate
affinities
with
CYP3A4,
is
critical
determinant
clearance,
interindividual
variability
disposition
clinical
efficacy,
appears
to
be
involved
mechanism
numerous
clinically
relevant
DDIs,
including
those
involving
dexamethasone.
recent
increase
use
high
doses
dexamethasone
during
COVID-19
pandemic
have
emphasized
need
for
better
knowledge
significance
setting.
We
therefore
aimed
review
already
published
evidence
various
DDIs
vitro
cell
culture
systems
vivo
animal
models
humans.
Language: Английский
Pharmacovigilance of Drug–Drug Interactions with Nirmatrelvir/Ritonavir
Infectious Diseases and Therapy,
Journal Year:
2024,
Volume and Issue:
unknown
Published: Oct. 26, 2024
Language: Английский
Dosing recommendation of nirmatrelvir/ritonavir using an integrated population pharmacokinetic analysis
CPT Pharmacometrics & Systems Pharmacology,
Journal Year:
2023,
Volume and Issue:
12(12), P. 1897 - 1910
Published: Oct. 6, 2023
Abstract
Protease
inhibitor
nirmatrelvir
coadministered
with
ritonavir
as
a
pharmacokinetic
enhancer
(PAXLOVID™;
Pfizer
Inc)
became
the
first
orally
bioavailable
antiviral
agent
granted
Emergency
Use
Authorization
in
United
States
patients
≥12
years
old
mild
to
moderate
coronavirus
disease
2019
(COVID‐19).
This
population
analysis
used
pooled
plasma
concentrations
from
eight
completed
phase
I
and
II/III
studies
characterize
pharmacokinetics
when
adults
with/without
COVID‐19.
Influence
of
covariates
(e.g.,
formulation,
dose,
COVID‐19)
was
examined
using
stepwise
forward
selection
(α
=
0.05)
backward
elimination
0.001)
approach.
Simulations
5000
subjects
for
each
age
weight
group
renal
function
category
were
performed
support
dosing
recommendations
nirmatrelvir/ritonavir
COVID‐19
guide
dose
adjustments
specific
patient
populations
insufficiency,
pediatrics).
The
final
model
two‐compartment
first‐order
absorption,
including
allometric
scaling
body
dose‐dependent
absorption
(power
on
relative
bioavailability).
Nirmatrelvir
clearance
(CL)
increased
proportionally
surface
area–normalized
creatinine
CL
(nCLCR)
up
70
ml/min/1.73
m
2
independent
nCLCR
above
breakpoint.
Significant
included
carbamazepine
or
itraconazole
coadministration
markers
drug
interactions,
CL,
formulation
bioavailability,
central
volume
distribution.
Simulation
results
current
300/100
mg
twice
daily
(b.i.d.)
normal
impairment
pediatrics
(12
<18
years)
weighing
≥40
kg
150/100
b.i.d.
impairment.
Language: Английский
Cardiovascular Drug Interactions with Nirmatrelvir/Ritonavir for COVID-19: Considerations for Daily Practice
European Cardiology Review,
Journal Year:
2024,
Volume and Issue:
19
Published: Aug. 9, 2024
Cardiovascular
disease
is
associated
with
progression
to
severe
COVID-19
and
patients
the
condition
are
among
those
in
whom
early
antiviral
therapy
should
be
warranted.
The
combination
of
nirmatrelvir/ritonavir
(Paxlovid®)
has
been
approved
for
clinical
use
by
Food
Drug
Administration
European
Medicines
Agency.
Because
cardiovascular
often
on
polypharmacy,
physicians
need
aware
potential
drug-drug
interactions
(DDIs)
when
treating
nirmatrelvir/ritonavir.
Guidance
given
avoiding
DDIs,
emphasising
that
preventing
managing
DDIs
requires
thorough
assessment
knowledge.
present
review
summarises
pharmacology
provides
details
a
focus
daily
practice
disease.
Particular
attention
needed
drugs
predominantly
metabolised
cytochrome
P450
3A4,
substrates
P-glycoprotein
have
narrow
therapeutic
index.
Proper
management
must
balance
benefit
nirmatrelvir/
ritonavir
prevent
risk
serious
adverse
events.
Language: Английский
Population pharmacokinetics of nirmatrelvir/ritonavir in critically ill Chinese COVID-19 patients and recommendations for medication use: a two-center retrospective study
Expert Review of Clinical Pharmacology,
Journal Year:
2024,
Volume and Issue:
17(11), P. 1071 - 1079
Published: Sept. 26, 2024
This
study
aimed
to
establish
population
pharmacokinetics
(PPK)
models
of
nirmatrelvir/ritonavir
in
critically
ill
Chinese
patients
with
the
coronavirus
disease
2019
(COVID-19)
infection,
explore
factors
affecting
(PK)
nirmatrelvir/ritonavir.
Language: Английский
Antiseizure medications
Mei T. Liu,
No information about this author
Daniel Greer,
No information about this author
Megan Maroney
No information about this author
et al.
Side effects of drugs annual,
Journal Year:
2024,
Volume and Issue:
unknown, P. 69 - 111
Published: Jan. 1, 2024
Development and Implementation of a Comprehensive Initiative to Educate Healthcare Providers and Patients in the United States about the Risk of Drug-Drug Interactions Associated with Nirmatrelvir/ritonavir during the COVID-19 Pandemic
Journal of Pharmaceutical Innovation,
Journal Year:
2024,
Volume and Issue:
19(5)
Published: Sept. 28, 2024
Language: Английский