Your browser version may not work well with NCBI's Web applications. More information here...
1: Br J Clin Pharmacol. 2005 Mar;59(3):310-3.Click here to read Click here to read Links

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

van Kan HJ, Groeneveld GJ, Kalmijn S, Spieksma M, van den Berg LH, Guchelaar HJ.

Academic Medical Centre, Department of Clinical Pharmacy, Meibergdreef 9, PO Box 22660, 1100 DD Amsterdam, The Netherlands. h.j.vankan@amc.uva.nl

AIMS: Riluzole 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. METHODS: A 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. RESULTS: Riluzole 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 r2 = 0.369). CONCLUSIONS: The 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.

PMID: 15752377 [PubMed - indexed for MEDLINE]

PMCID: PMC1884790

Patient Drug Information

  • Theophylline (Bronkodyl® , Elixophyllin® , Slo-bid® , ...)

    Theophylline is used to prevent and treat wheezing, shortness of breath, and difficulty breathing caused by asthma, chronic bronchitis, emphysema, and other lung diseases. It relaxes and opens air passages in the lungs, ...

  • Riluzole (Rilutek® )

    Riluzole is used to slow the progress of amyotrophic lateral sclerosis (ALS or Lou Gehrig's disease). The drug also may delay the need for a tracheostomy (breathing tube), but it is not a cure for ALS.

  • Source: AHFS Consumer Medication Information