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.