Effect of phenytoin, phenobarbital and valproic acid oncarbamazepine clearance and therapeutic out come:derived from routine therapeutic drug monitoringdata at Prasat Neurological Institute
Background : Pharmacokinetics (PK) of carbamazepine (CBZ) are highly variable andfurther complicated by concomitant use of other antiepileptic drugs withinduction or inhibition properties.Objective : To determine the pharmacokinetics of CBZ when used as monotherapyor co-administrated with phenytoin (PHT), phenobarbital (PB) or valproicacid (VPA) along with the related therapeutic outcome.Design : A descriptive study.Setting : Prasat Neurological Institute, Bangkok.Patients : Patients aged more than 13 years old with epilepsy or other neurologicaldisease who used CBZ as monotherapy or co-administrated with PHT,PB or VPA and their therapeutic drug monitoring data (TDM) had beenrecorded and available were included into this study.Method : Four-year retro-prospective data, August 2006 - August 2010, werecollected from electronic database and medical records of the outpatientepilepsy clinic.Result : Data of 74 patients, 34 men and 40 women, were identified and used inthis analysis; 71 were diagnosed with epilepsy while 3 had neuropathicpain. Their age were ranged from 13.87 to 82.05 years (mean = 40.13 ±15.22). The median level - to - dose ratio of CBZ in patients who usedCBZ as monotherapy (10.88 mcg/L/mg, N = 30) was significantly higher(p < 0.001) than those obtained after combination therapy with PHT(6.13 mcg/L/mg, N =15), PB (6.81 mcg/L/mg, N =14) or VPA (8.88 mcg/L/mg, N =15), even though the median daily dose of CBZ (13.36 VS16.47, 16.88 and 16.02 mg/kg/day, respectively) was not significantlydifferent (p = 0.184). The median clearance of CBZ in patients whoused CBZ in combination with PHT (2.34 L/kg/day) or PB (1.49 L/kg/day)was significantly higher than that observed after CBZ monotherapy(1.09 L/kg/day) (p < 0.001 and p = 0.013, respectively). However, themedian clearance of CBZ in patients who used CBZ in combination withVPA (1.34 L/kg/day) was not significantly different from that found aftermonotherapy (p = 0.118). Seventeen patients (24%) of the 71 epilepticpatients participated had uncontrolled seizure while 4 patients (6%) hadmild adverse effects.Conclusion : The clearance of CBZ in patients who used CBZ as monotherapy wassignificantly lower than in those observed patients who used CBZ incombination with PHT or PB, but it was not significantly different frompatients who used CBZ in combination with VPA.
Faculty of Medicine, Chulalongkorn University
Traiyawong, T; Panomvanna, D; and Towanabut, S.
"Effect of phenytoin, phenobarbital and valproic acid oncarbamazepine clearance and therapeutic out come:derived from routine therapeutic drug monitoringdata at Prasat Neurological Institute,"
Chulalongkorn Medical Journal: Vol. 55:
4, Article 2.
Available at: https://digital.car.chula.ac.th/clmjournal/vol55/iss4/2