Introduction
Pregabalin is an anti-epileptic drug representing one of the most
frequently prescribed medications for neuropathic pain management
worldwide, whereas its use as an anti-convulsant is currently limited
[1]. Despite being an analogue of the inhibitory neurotransmitter
gamma-aminobutyric acid (GABA), like gabapentin, pregabalin shows no
binding activity to GABA receptors. Instead, it binds with high affinity
to the alpha-2-delta subunit of voltage-gated calcium channels, located
at neuronal presynaptic endings at different levels in the nervous
system, decreasing the depolarization-induced influx of calcium into
neurons and ultimately reducing the synaptic release of excitatory
neurotransmitters [2]. The reduction of abnormal neuronal
excitability within the brain may account for its anticonvulsant and
anxiolytic effects, while a decrease in synaptic release of several
neuromediators at the spinal cord level, such as glutamate, Calcitonin
gene-related peptide (CGRP), and substance P, is likely to be
responsible for its analgesic effects [2]. Pregabalin is available
in US and Europe as capsules (25 mg, 50 mg, 75 mg, 100 mg, 150 mg, 200
mg, 225 mg, 300 mg) and as an oral solution (20 mg/ml), with recommended
doses between 150 mg and 600 mg a day, split into 2 or 3 separate doses.
Extended-release tablets for single daily administration are also
available (82.5 mg, 165 mg, 330 mg) [2]. It has rapid absorption
following oral administration, with peak plasma concentrations occurring
between 0.7 and 1.3 hours, and shows 90% bioavailability, independently
of dose and administration frequency. Half-life is approximately 6
hours, with steady state achievement within 1 to 2 days [3, 4]. It
mainly undergoes renal elimination (98% as unchanged drug), and
posology adjustments are needed in patients with kidney failure
(Table 1 ) [5]. Side effects are less severe respect to
other anti-epileptic drugs, being the most frequently reported
somnolence, dizziness, dry mouth, angioedema, blurred vision, and weight
gain [1]. Pregabalin is currently approved in US and Europe for the
treatment of neuropathic pain deriving from diabetic neuropathy,
post-herpetic neuralgia, and spinal cord injury, besides being
recognized as an adjunctive therapy of partial-onset seizures in adults.
Therapeutic indications have been expanded to generalized and social
anxiety disorders, whereas only in the US it is FDA-approved for the
treatment of fibromyalgia syndrome [6]. Off-label pregabalin uses
include bipolar disorder, insomnia, restless legs syndrome, and chronic
pain conditions other than those above listed, such as cancer pain and
post-surgical pain [6]. Patients with Chronic Kidney Disease (CKD)
often take pregabalin with heterogeneous therapeutical indications, such
as neuropathic pain, pruritus, and restless legs syndrome [7]. Not
least, pregabalin is gaining an emerging role for pre-emptive
preoperative multimodal analgesia, with different randomized clinical
trials showing its efficacy in reducing post-operatory pain and opioid
consumption after different types of surgical interventions [8, 9].
Mostly in this context, given the pharmacokinetic profile of pregabalin,
the start of Kidney Replacement Therapy (KRT) for Acute Kidney Injury
(AKI) usually adds further complexity related to the additional
extracorporeal clearance. Despite the limited available data, the
implementation of the use of Therapeutic Drug Monitoring (TDM) of
pregabalin may represent a useful tool to accurately tailor the
pharmacological prescription [10-12].
We report here a case of a critically ill patient undergoing different
KRT modalities for severe AKI in whom pregabalin levels in the course of
different modalities were monitored by TDM.