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More than 95% of the dose appears in the urine, with less than 1% as unchanged oxcarbazepine. Fecal excretion accounts for less than 4% of the administered dose. Approximately 80% of the dose is excreted in the urine either as glucuronides of MHD (49%) or as unchanged MHD (27%); the inactive DHD accounts for approximately 3% and conjugates of MHD and oxcarbazepine account for 13% of the dose. The half-life of the parent is about 2 hours, while the half-life of MHD is about 9 hours. Following administration of single (300 mg) and multiple (600 mg/day) doses of TRILEPTAL to elderly volunteers (60 to 82 years of age), the maximum plasma concentrations and AUC values of MHD were 30% to 60% higher than in younger volunteers (18 to 32 years of age). Comparisons of creatinine clearance in young and elderly volunteers indicate that the difference was due to age-related reductions in creatinine clearance. Weight-adjusted MHD clearance decreases as age and weight increases, approaching that of adults. The mean weight-adjusted clearance in children 2 years to AED Coadministered Dose of AED (mg/day) TRILEPTAL Dose (mg/day) Influence of TRILEPTAL on AED Concentration (Mean Change, 90% Confidence Interval) Influence of AED on MHD Concentration (Mean Change, 90% Confidence Interval) Carbamazepine 400-2000 900 nc 1 40% decrease [CI: 17% decrease, 57% decrease] Phenobarbital 100-150 600-1800 14% increase [CI: 2% increase, 24% increase] 25% decrease [CI: 12% decrease, 51% decrease] Phenytoin 250-500 600-1800 >1200-2400 nc 1,2 up to 40% increase 3 [CI: 12% increase, 60% increase] 30% decrease [CI: 3% decrease, 48% decrease] Valproic acid 400-2800 600-1800 nc 1 18% decrease [CI: 13% decrease, 40% decrease] Lamotrigine 200 1200 nc 1 nc 1 1 nc denotes a mean change of less than 10% 2 Pediatrics 3 Mean increase in adults at high TRILEPTAL doses. Coadministration of TRILEPTAL with an oral contraceptive has been shown to influence the plasma concentrations of the two hormonal components, ethinylestradiol (EE) and levonorgestrel (LNG) [see DRUG INTERACTIONS ]. The mean AUC values of EE were decreased by 48% [90% CI: 22 to 65] in one study and 52% [90% CI: 38 to 52] in another study. The mean AUC values of LNG were decreased by 32% [90% CI: 20 to 45] in one study and 52% [90% CI: 42 to 52] in another study. Calcium Antagonists: After repeated coadministration of TRILEPTAL, the AUC of felodipine was lowered by 28% [90% CI: 20 to 33], prime anabolics review australia. Verapamil produced a decrease of 20% [90% CI: 18 to 27] of the plasma levels of MHD. Cimetidine, erythromycin and dextropropoxyphene had no effect on the pharmacokinetics of MHD. Results with warfarin show no evidence of interaction with either single or repeated doses of TRILEPTAL. The effectiveness of TRILEPTAL as adjunctive and monotherapy for partial seizures in adults, and as adjunctive therapy in children aged 2 to 16 years was established in seven multicenter, randomized, controlled trials. The effectiveness of TRILEPTAL as monotherapy for partial seizures in children aged 4 to 16 years was determined from data obtained in the studies described, as well as by pharmacokinetic/pharmacodynamic considerations. Four randomized, controlled, double-blind, multicenter trials, conducted in a predominately adult population, demonstrated the efficacy of TRILEPTAL as monotherapy. Two trials compared TRILEPTAL to placebo and 2 trials used a randomized withdrawal design to compare a high dose (2400 mg) with a low dose (300 mg) of TRILEPTAL, after substituting TRILEPTAL 2400 mg/day for 1 or more antiepileptic drugs (AEDs). All doses were administered on a twice-a-day schedule. A fifth randomized, controlled, rater-blind, multicenter study, conducted in a pediatric population, failed to demonstrate a statistically significant difference between low and high dose TRILEPTAL treatment groups. One placebo-controlled trial was conducted in 102 patients (11 to 62 years of age) with refractory partial seizures who had completed an inpatient evaluation for epilepsy surgery. Patients had been withdrawn from all AEDs and were required to have 2 to 10 partial seizures within 48 hours prior to randomization. Patients were randomized to receive either placebo or TRILEPTAL given as 1500 mg/day on Day 1 and 2400 mg/day thereafter for an additional 9 days, or until 1 of the following 3 exit criteria occurred: 1) the occurrence of a fourth partial seizure, excluding Day 1, 2) 2 new-onset secondarily generalized seizures, where such seizures were not seen in the 1-year period prior to randomization, or 3) occurrence of serial seizures or status epilepticus. 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