title: The effect of poor compliance on the pharmacokinetics of carbamazepine and its epoxide metabolite using Monte Carlo simulation.
abstract: OBJECTIVE
  To study the effects of delayed and missed doses (poor compliance) on the pharmacokinetics of carbamazepine (CBZ) and its main active metabolite carbamazepine-10,11-epoxide (CBZE) in Chinese epilepsy patients using Monte Carlo simulation.
  
  
  METHODS
  CBZ and CBZE time-concentration profiles in various scenarios were generated based on a population pharmacokinetic study in Chinese epilepsy patients using Monte Carlo simulation. The scenarios included patients given multiple doses of CBZ that ranged from 100 to 300 mg three times daily or from 200 to 300 mg every 12 h. The therapeutic range of CBZ and CBZE for each scenario was estimated to assess the effect of delayed or missed doses and to design corresponding rescue regimens. Moreover, the impact of body weight, absorption rate and co-therapy with other antiepileptic drugs (phenytoin, phenobarbital and valproic acid) on the dosage recommendation was investigated in the event of poor compliance.
  
  
  RESULTS
  The risk for a sub-therapeutic range of CBZ and CBZE was increased in a dose-dependent manner in both two and three times daily regimens when delayed or missed doses occurred. The effects of poor compliance was less prominent on the lower daily doses compared with those on the higher daily doses. The dose recommendations, in the event of poor compliance, were time related and dose dependent. Patient body weight, absorption rate and co-therapy with phenytoin, phenobarbital and valproic acid had no significant impact on the dose recommendation.
  
  
  CONCLUSIONS
  Patients with epilepsy should take the delayed doses as soon as they remember, and partial missed doses may need to be taken near or at the next scheduled time.
authors.affiliation: Children's Hospital of Fudan University, Shanghai, China.
authors.forename: Jun-jie
authors.initials: JJ
authors.lastname: Ding
authors.forename: Yun-jian
authors.initials: YJ
authors.lastname: Zhang
authors.forename: Zheng
authors.initials: Z
authors.lastname: Jiao
authors.forename: Yi
authors.initials: Y
authors.lastname: Wang
mesh_terms: D000927:Anticonvulsants / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000627:therapeutic use; D044466:Asian People; D002220:Carbamazepine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics* / Q000627:therapeutic use; D002681:China; D003198:Computer Simulation; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004347:Drug Interactions; D004827:Epilepsy / Q000188:drug therapy; D006801:Humans; D055118:Medication Adherence; D009010:Monte Carlo Method; D013997:Time Factors
chemical_list: D000927:Anticonvulsants; D002220:Carbamazepine; C012227:carbamazepine epoxide