A validated HPLC assay to monitor riluzole plasma or serum concentrations in patients with amyotrophic lateral sclerosis

Kan, H. J. M. van; Spieksma, M.; Groeneveld, Geert Jan; Toraño, Javier Sastre; Berg, Leonard H. van den; Guchelaar, Henk‐Jan

doi:10.1002/bmc.384

Cited by 20 publications

(12 citation statements)

References 5 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…21 Briefly, this assay has a between-run imprecision of 1.8-9.7%, and an accuracy of 102-103% within the quantification range of 20-2,000 ng/ml. In the week before blood sampling, all patients were asked to take riluzole at exactly 1000 and 2200 hours.…”

Section: Discussionmentioning

confidence: 99%

An Association Study of Riluzole Serum Concentration and Survival and Disease Progression in Patients With ALS

Groeneveld

Kan

Lie‐A‐Huen

et al. 2007

Clin Pharmacol Ther

View full text Add to dashboard Cite

Patients with amyotrophic lateral sclerosis (ALS) who are treated with the antiglutamatergic drug riluzole receive a fixed-dose regimen of 50 mg b.i.d. The drug has been shown to increase tracheostomy-free survival by 3-6 months. The pharmacokinetics of riluzole show a high interindividual variability. Riluzole serum concentrations are associated with side effects and ALS symptoms, but the effect of the actual blood level of riluzole on disease progression and survival is unknown. We measured trough and peak serum concentrations of riluzole in 160 patients with ALS, and estimated the area under the curve for one dosage interval (AUCi) using a Bayesian method. We then determined the association between riluzole AUCi and survival over a 5-year period, and between riluzole AUCi and disease progression, defined by the rates of decline of arm strength and vital lung capacity. No significant association was found between riluzole AUCi and survival or disease progression.

show abstract

Section: Discussionmentioning

confidence: 99%

An Association Study of Riluzole Serum Concentration and Survival and Disease Progression in Patients With ALS

Groeneveld

Kan

Lie‐A‐Huen

et al. 2007

Clin Pharmacol Ther

View full text Add to dashboard Cite

show abstract

“…54 With a standard drug regimen of 50 mg twice daily, riluzole serum concentrations are in the range of 20-250 ng/ml. 19 The plasma samples retaining clotting factors will have less variability than serum samples.…”

Section: Pharmacokinetic Evaluationmentioning

confidence: 99%

Pharmacology of riluzole in acute spinal cord injury

Chow

Teng

Toups

et al. 2012

SPI

View full text Add to dashboard Cite

Object The aim of this paper was to characterize individual and population pharmacokinetics of enterally administered riluzole in a Phase 1 clinical trial of riluzole as a neuroprotective agent in adults 18–70 years old with acute spinal cord injury (SCI). Methods Thirty-five individuals with acute SCI, American Spinal Injury Association Impairment Scale Grades A–C, neurological levels from C-4 to T-12, who were enrolled in the Phase 1 clinical trial sponsored by the North American Clinical Trials Network for Treatment of Spinal Cord Injury, received 50 mg riluzole twice daily for 28 doses. The first dose was administered at a mean of 8.7 ± 2.2 hours postinjury. Trough plasma samples were collected within 1 hour predose, and peak plasma samples were collected 2 hours postdose on Days 3 and 14 of treatment. Riluzole concentrations were quantified by high-performance liquid chromatography assay. The data were analyzed for individual and population pharmacokinetics using basic structural and covariate models. The pharmacokinetic measures studied were the peak concentration (Cmax), trough concentration (Cmin), systemic exposure (AUC0–12), clearance (CL/F), and volume of distribution (V_F) normalized by the bioavailability (F). Results The Cmax and AUC0–12 achieved in SCI patients were lower than those in ALS patients on the same dose basis, due to a higher CL and larger V. The pharmacokinetics of riluzole (Cmax, Cmin, AUC0–12, CL, and V) changed during the acute and subacute phases of SCI during the 14 days of therapy. It was consistently observed in patients at all clinical sites that Cmax, Cmin, and AUC0–12 (128.9 ng/ml, 45.6 ng/ml, and 982.0 ng × hr/ml, respectively) were significantly higher on Day 3 than on Day 14 (76.5 ng/ml, 19.1 ng/ml, and 521.0 ng × hr/ml, respectively). These changes resulted from lower CL (49.5 vs 106.2 L/hour) and smaller V (557.1 vs 1297.9/L) on Day 3. No fluid imbalance or cytochrome P 1A2 induction due to concomitant medications was identified during the treatment course to account for such increases in V and CL, respectively. Possible mechanisms underlying these changes are discussed. Conclusions This is the first report of clinical pharmacokinetics of riluzole in patients with SCI. The Cmax and AUC0–12 achieved in SCI patients were lower than those in ALS patients on the same dose basis, due to a higher clearance and larger volume of distribution in SCI patients. The finding in SCI patients of an increase in the clearance and distribution of riluzole between the 3rd and 14th days after SCI, with a lower plasma concentration of riluzole on the 14th day, stresses the importance of monitoring changes in drug metabolism after SCI in interpreting the safety and efficacy of therapeutic drugs that are used in clinical trials in SCI. Clinical trial registration no.: NCT00876889.

show abstract

“…To estimate riluzole clearance, 2 h post dose and trough serum concentrations of riluzole were measured using a validated liquid chromatographic assay with ultraviolet detection in venous blood samples collected at weekly intervals (quantification range: 0.020–2.00 µg ml −1 ; between‐run coefficient of variation: 1.8–9.7%) [16]. From at least one 2 h and one trough concentration per patient, riluzole clearances were estimated using a Bayesian fitting procedure (Marquardt algorithm) performed with MW/Pharm v3.50 software (MediWare, Zuidlaren, the Netherlands) [17].…”

Section: Methodsmentioning

confidence: 99%

Association between CYP1A2 activity and riluzole clearance in patients with amyotrophic lateral sclerosis

Kan

Groeneveld

Kalmijn

et al. 2005

Brit J Clinical Pharma

Self Cite

View full text Add to dashboard Cite

AimsRiluzole is used in a fixed dosing schedule of 50 mg twice daily to treat patients with amyotropic lateral sclerosis (ALS), one form of motor neurone disease. The large variability in the pharmacokinetics of riluzole may be a factor contributing to its limited therapeutic benefit. Riluzole is assumed to be mainly metabolized by the cytochrome P450 enzyme 1A2 (CYP1A2). The aim of the study was to investigate the relationship between CYP1A2 activity and riluzole clearance with a view to optimize drug treatment. MethodsA group of 30 ALS patients participated in the study. In each patient the CYP1A2 activity was determined using caffeine as a metabolic probe. Riluzole clearance was estimated from serum drug concentration measurements followed by Bayesian fitting. ResultsRiluzole clearance and the serum paraxanthine : caffeine (P/C) ratio showed a positive correlation ( r = 0.693; P = 0.0002). Linear regression analysis identified the P/C ratio (beta: 1.16) and height (beta: 0.027) as independent predictors of riluzole clearance (adjusted r 2 = 0.369). ConclusionsThe P/C ratio, used as measure of CYP1A2 activity, significantly correlated with the riluzole clearance, although only 37% of the observed variability could be explained.

show abstract

A validated HPLC assay to monitor riluzole plasma or serum concentrations in patients with amyotrophic lateral sclerosis

Cited by 20 publications

References 5 publications

An Association Study of Riluzole Serum Concentration and Survival and Disease Progression in Patients With ALS

An Association Study of Riluzole Serum Concentration and Survival and Disease Progression in Patients With ALS

Pharmacology of riluzole in acute spinal cord injury

Association between CYP1A2 activity and riluzole clearance in patients with amyotrophic lateral sclerosis

Contact Info

Product

Resources

About