Morphine is a widely used opioid analgesic, which shows large differences in clinical
response in children, even when aiming for equivalent plasma drug concentrations. Age …

Pharmacokinetics (PK)–pharmacodynamics (PD) modeling, the mathematical description of
the relationship between PK and PD, can estimate and predict relevant parameters …

Abstract Morphine and morphine-6-glucuronide (M6G) produce central nervous system
(CNS) effects by activating mu-opioid receptors, while naloxone is used mainly for the …

Background and purpose: Biophase equilibration must be considered to gain insight into the
mechanisms underlying the pharmacokinetic‐pharmacodynamic (PK‐PD) correlations of …

ABSTRACT A whole-body physiologically based pharmacokinetic (PBPK) model was
developed for the prediction of unbound drug concentration-time profiles in the rat brain, in …

Morphine blood-brain barrier (BBB) transport is governed by passive diffusion, active efflux
and saturable active influx. This may result in nonlinear plasma concentration-dependent …

Central nervous system drug discovery and development is hindered by the impermeable
nature of the blood–brain barrier. Pharmacokinetic modeling can provide a novel approach …

Morphine has large pharmacokinetic variability, which is further complicated by
developmental changes in neonates and small infants. The impacts of organic cation …

The pharmacokinetics (PK) of morphine has been extensively investigated. Though different
publications have focused on the various aspects of morphine PK, none have quantitatively …

Morphine shows large interindividual variability in its pharmacokinetics; however, the cause
of this has not been fully addressed. The variability in morphine disposition is considered to …