Experience from therapeutic drug monitoring and gender aspects of gabapentin and pregabalin in clinical practice

Landmark, Cecilie Johannessen; Beiske, Georg; Baftiu, Arton; Burns, Margrete Larsen; Johannessen, Svein I.

doi:10.1016/j.seizure.2015.02.017

Cited by 41 publications

(18 citation statements)

References 11 publications

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“…These results are consistent with the reported studies related to pharmacokinetic variability of pregabalin which emphasize that pregabalin has extensive pharmacokinetic variability and that age and gender are contributing factors of this variability which elucidates the need for individualization of therapy and TDM [27,28]. ▶table 1 Steady state trough and maximum plasma and saliva pregabalin levels (ng/ml) in 44 patients enrolled in this study.…”

Section: Resultssupporting

confidence: 90%

Saliva versus Plasma Therapeutic Drug Monitoring of Pregabalin in Jordanian Patients

et al. 2018

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The objective is using saliva instead of plasma for pregabalin therapeutic drug monitoring (TDM) since saliva reflects the free non-protein bound drug concentration, simple and noninvasive sampling, cheaper and does not require the expertise of drawing blood. Forty four patients participated in this study, two samples of saliva and another two of blood were taken from each patient; first sample of both saliva and blood is the trough sample and was taken just before the first dose of the day and second sample is the peak sample and was taken 1 h after taking the first dose of the day. Descriptive statistics and t-testing after log transformation were done using Excel, p-value=0.05 was adopted for significant difference. Optimized effective intestinal permeability of pregabalin was estimated by PK-Sim program version 7. This study for the first time revealed that pregabalin is excreted in saliva and classified as class 1 based on Salivary Excretion Classification System (SECS). A good correlation of 0.71-0.83 between Cmin and Cmax of plasma and saliva pregabalin was observed respectively which indicate that saliva sampling is a good alternative matrix for pregabalin TDM. C/D-ratios were calculated to demonstrate pharmacokinetic variability of Pregabalin; the results showed that C/D-ratio was higher in women, elderly and in those patients who had Scr.≥0.9 mg/dl. Proposed pregabalin therapeutic ranges are 0.7 to 1.84 µg/ml in plasma and 0.055 to 0.145 µg/ml in saliva, for neuropathic pain, diabetic neuropathy and disc prolapse patients.

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Section: Resultssupporting

confidence: 90%

Saliva versus Plasma Therapeutic Drug Monitoring of Pregabalin in Jordanian Patients

et al. 2018

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“…We found extensive pharmacokinetic variability among the included patients as demonstrated by the 22-fold range in C/D ratios, in line with the known variability in bioavailability, 11 the effect of renal function on clearance 28 and previous findings from clinical practice. 29 The observation that the C/D ratio was higher in elderly patients (≥65 years) also confirms previous findings. 29,30 It has been suggested that changes in renal function are responsible for age-related changes in GBP pharmacokinetics, 28 but as we did not have information on renal function at the time of serum concentration measurement, we could not examine this.…”

Section: Pharmacokinetic Variability From Retrospective Tdm Datasupporting

confidence: 88%

“…29 The observation that the C/D ratio was higher in elderly patients (≥65 years) also confirms previous findings. 29,30 It has been suggested that changes in renal function are responsible for age-related changes in GBP pharmacokinetics, 28 but as we did not have information on renal function at the time of serum concentration measurement, we could not examine this.…”

Section: Pharmacokinetic Variability From Retrospective Tdm Datasupporting

confidence: 88%

Therapeutic drug monitoring of gabapentin in various indications

et al. 2019

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Objectives Gabapentin has been increasingly used in various indications in recent years. Despite variable pharmacokinetics, therapeutic drug monitoring (TDM) is scarcely described in other indications than epilepsy. The aim of the study was to investigate the use and pharmacokinetic variability of gabapentin in epilepsy and non‐epilepsy indications and to further evaluate the use of TDM in patients with restless legs syndrome (RLS). Materials & Methods Population‐based data from the Norwegian Prescription Database, retrospective TDM data from the section for Clinical Pharmacology, the National Center for Epilepsy, Norway, and prospective observational data on patients with RLS were used. Results The use of gabapentin increased by 30% from 2014 to 2017 (32 181 to 42 675 users). TDM data from 120 patients showed a 22‐fold pharmacokinetic variability in concentration/dose ratios, and this ratio was elevated in elderly patients (≥65 years). The majority of elderly used gabapentin for non‐epilepsy indications. In patients with RLS, intake in the evening/night only was common due to nocturnal symptoms, in contrast to regular dosing regimens in epilepsy. Thus, drug fasting concentrations do not reflect concentrations at the time of required therapeutic effect. TDM was still found useful in most patients to support dosage increase or evaluate adverse effects. Conclusion Due to extensive pharmacokinetic variability, TDM can benefit patients using gabapentin. Challenges with applying TDM in new indications such as RLS include different dosage regimens and consequently different interpretation of serum concentrations. Thus, TDM should be requested on clear clinical grounds and the service tailored according to the therapeutic indication.

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“…HVA calcium channels may also be targeted for the treatment of seizures. Gabapentin is used as an anticonvulsant to treat focal and partial seizures 148 . However, given that this compound has the propensity to affect multiple types of HVA channels through its interaction with Cavα2δ subunits, it is not clear how this compound mediates its clinical effects at the cellular level.…”

Section: Lamotriginementioning

confidence: 99%

Targeting voltage-gated calcium channels in neurological and psychiatric diseases

Zamponi

2015

Nat Rev Drug Discov

337

331

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Voltage-gated calcium channels are important regulators of brain, heart and muscle functions, and their dysfunction can give rise to pathophysiological conditions ranging from cardiovascular disorders to neurological and psychiatric conditions such as epilepsy, pain and autism. In the nervous system, calcium channel blockers have been used successfully to treat absence seizures, and are emerging as potential therapeutic avenues for pathologies such as pain, Parkinson disease, addiction and anxiety. This Review provides an overview of calcium channels as drug targets for nervous system disorders, and discusses potential challenges and opportunities for the development of new clinically effective calcium channel inhibitors.

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Experience from therapeutic drug monitoring and gender aspects of gabapentin and pregabalin in clinical practice

Abstract: Gabapentin and pregabalin are more used in women than in men, and routine use of TDM is most common in patients with epilepsy. Pharmacokinetic variability is extensive, highlighting a need for individualisation of therapy regardless of indication.

Cited by 41 publications

References 11 publications

Saliva versus Plasma Therapeutic Drug Monitoring of Pregabalin in Jordanian Patients

Saliva versus Plasma Therapeutic Drug Monitoring of Pregabalin in Jordanian Patients

Therapeutic drug monitoring of gabapentin in various indications

Targeting voltage-gated calcium channels in neurological and psychiatric diseases

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