Pregabalin effect on steady‐state pharmacokinetics of carbamazepine, lamotrigine, phenobarbital, phenytoin, topiramate, valproate, and tiagabine

Abstract

SUMMARYBy reducing neuronal excitability through selective binding to the a 2 d subunit of voltage-dependent calcium channels, pregabalin effectively treats epilepsy, chronic pain, and anxiety disorders. To evaluate if pregabalin coadministration affects pharmacokinetics of other antiepileptic drugs, population pharmacokinetic analyses using NONMEM software were performed on data from three epilepsy trials involving seven antiepileptic drugs with pregabalin as add-on therapy. Results demonstrated that pregabalin did not alter the steadystate plasma concentrations of carbamazepine, lamotrigine, phenobarbital, phenytoin, tiagabine, topiramate, and valproate. Furthermore, the small percent change in the population estimate of antiepileptic drug plasma clearance values ()2% to +7%) suggests that pregabalin coadministration exerted no significant effect on the pharmacokinetics of these antiepileptic drugs, with the possible exception of tiagabine (+34.9%). These findings are in agreement with those of previously published reports. A further clarification study is necessary for tiagabine. In conclusion, it appears that pregabalin can be coadministered with other antiepileptic drugs without concern for significantly altering their pharmacokinetic profiles. KEY WORDS: Pregabalin, Antiepileptic drugs, Anticonvulsants, Coadministration, Population pharmacokinetics.Pregabalin is a selective, high-affinity ligand for a novel central nervous system binding site, the a 2 d subunit of voltage-dependent calcium channels (Gee et al., 1996). The ability of pregabalin to decrease neuronal excitability by selectively attenuating presynaptic calcium influx through these channels Fink et al., 2002) may underlie its efficacy in patients with partial seizures (French et al., 2003;Miller et al., 2003), chronic pain disorders (Iacobellis et al., 2000;Glessner et al., 2001;Crofford et al., 2002;Dworkin et al., 2003), and generalized anxiety disorder Pande et al., 2003). A population pharmacokinetic analysis (Bockbrader et al., 2010) was performed to characterize pregabalin pharmacokinetics in healthy volunteers (Corrigan et al., 2001), patients with various chronic pain disorders, and patients with epilepsy who participated in a series of phase 3 add-on trials. The analyses revealed that pregabalin pharmacokinetics were similar in the different populations (Randinitis et al., 2003). Furthermore, concomitant anticonvulsant medications, including carbamazepine, lamotrigine, phenobarbital, phenytoin, tiagabine, topiramate, and valproate, had no effect on the pharmacokinetics of pregabalin.The purpose of the present study was to determine the effect of pregabalin on the pharmacokinetics of commonly used antiepileptic drugs (AEDs) in patients with partial seizures. Plasma concentrations of carbamazepine, lamotrigine, phenobarbital, phenytoin, tiagabine, topiramate, and valproate were determined prior to and during pregabalin administration in the phase 3 add-on epilepsy trials, and were utilized to determine if pregabalin coadministration had ...

A Review of Pregabalin for the Treatment of Peripheral and Central Neuropathic Pain and Its Place in the Treatment of Chronic Pain

“…24 In vivo studies suggest that the coadministration of pregabalin does not affect the pharmacokinetics of gabapentin, oral contraceptives, lorazepam, oxycodone, ethanol, and, with the possible exception of tiagabine, other antiepileptic drugs to a relevant extent. 20,25 …”

Pregabalin Addiction: Case Report of a Young Adult

“…22 Similarly, in a population of former prisoners, those with disorders related to opioid use were more likely to abuse pregabalin (26%) than those with a disorder related to the use of non-opioid substances (4%). [23][24][25][26] In most cases, pregabalin is initially been prescribed to treat a medical condition, which suggests that the development of addictive behaviors associated with pregabalin may also occur in the context of normal medical treatment. Moreover, it is being used for many unapproved indications.…”

Clinically relevant drug interactions in anxiety disorders

“…Coadministration of pregabalin, 600 mg/day, for 7 days did not alter steady‐state concentrations of valproate (16 patients), phenytoin (11 patients), lamotrigine (12 patients), or carbamazepine (14 patients). These findings were confirmed by a recent population pharmacokinetic analysis showing that pregabalin did not affect plasma concentrations of carbamazepine, lamotrigine, phenobarbital, phenytoin, tiagabine, topiramate, and valproate (Bockbrader et al ., ).…”