title: Tolerability and pharmacokinetics of oral loading with lamotrigine in epilepsy monitoring units.
abstract: OBJECTIVE
  To investigate the tolerability and pharmacokinetics of oral loading with lamotrigine (LTG) among epilepsy patients after temporary drug discontinuation in an epilepsy monitoring unit.
  
  
  METHODS
  We conducted a pilot study among epilepsy patients (18 years or older) receiving maintenance doses of LTG. LTG was discontinued on admission and restarted at the end of epilepsy monitoring. LTG was given as a single oral dose calculated based on the population expected volume of distribution (Vd, 1.0 L/kg) and target blood level on admission. Baseline and serial blood levels of LTG were determined hourly for 10 to 12 h after the loading dose.
  
  
  METHODS
  (a) frequency of patients with side effects; (b) time to maximum concentration (Tmax), maximum concentration (Cmax), actual volume of distribution, and half-life.
  
  
  RESULTS
  Twenty-four patients received a single oral load of LTG (mean, 6.5 +/- 2.7 mg/kg). Overall, LTG loading was well tolerated with no serious adverse events or skin rash observed. Two patients had transient and mild nausea 1 to 2 h after the oral load. The mean estimated pharmacokinetic parameters are as follows: Tmax, 3.1 +/- 2.1 h; Cmax, 8.2 +/- 6.5 mg/L; Vd, 1.1 +/- 1.0 L/kg; clearance, 0.08 +/- 0.08 mg/L/h; half-life, 22 +/- 30 h. All patients reached their target blood levels.
  
  
  CONCLUSIONS
  Epilepsy patients temporarily discontinued from LTG can be restarted with a single oral loading dose. This was well tolerated, and therapeutic levels can be achieved within 1 to 3 h.
authors.affiliation: Department of Neurology, Cleveland Clinic Foundation, Cleveland, Ohio, USA. lardizd@ccf.org
authors.forename: David V
authors.initials: DV
authors.lastname: Lardizabal
authors.forename: Harold H
authors.initials: HH
authors.lastname: Morris
authors.forename: Collin A
authors.initials: CA
authors.lastname: Hovinga
authors.forename: Maria
authors.initials: M
authors.lastname: Del Mar Carreño
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000927:Anticonvulsants / Q000008:administration & dosage / Q000009:adverse effects* / Q000493:pharmacokinetics; D001682:Biological Availability; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D016903:Drug Monitoring; D004569:Electroencephalography / Q000187:drug effects*; D004827:Epilepsy / Q000097:blood / Q000188:drug therapy*; D005260:Female; D006207:Half-Life; D006801:Humans; D000077213:Lamotrigine; D008297:Male; D008875:Middle Aged; D008991:Monitoring, Physiologic; D010351:Patient Discharge; D010865:Pilot Projects; D013375:Substance Withdrawal Syndrome / Q000097:blood / Q000188:drug therapy / Q000209:etiology*; D014227:Triazines / Q000008:administration & dosage / Q000009:adverse effects* / Q000493:pharmacokinetics
chemical_list: D000927:Anticonvulsants; D014227:Triazines; D000077213:Lamotrigine