THERAPEUTIC DRUG MONITORING OF ANTICONVULSANTS IN CHILDREN IN CLINICAL PRACTICE

Objective. To study concentration of valproats in children with epilepsy, newborns  and infants with episyndrome  using therapeutic drug monitoring (TDM) in routine clinical practice. Materials and  methods. 75 children aged 1-18 years and 59 preterm newborns aged 0-90 days receiving valproic acid drugs were included in the study. Valproic acid concentration was measured using high performance liquid chromatography (HРLC). Results. Therapeutic concentration was achieved in 77.3%  of  children  aged  1-18  years  with  an  average  daily dose  of  25.94  mg/kg  (1021.4  mg);  overtherapeutic concentrations  were registered  in 9.3%  of the cases.  Concentration of valproic acid tended  to decrease  along with children’s age. Among children aged 1-18, a direct correlation between the daily dose (in mg/kg) and concentrations  of  valproates was observed: r=0.42 for Cmin and r=0.50 for Cmax. There was no correlation between age and concentration. In newborns,  therapeutic concentration  was achieved only in 33.9% of the cases  with an average daily dose  of 43.4 mg/kg  (82.6  mg); overtherapeutic  concentrations  were registered  in 11.9%  of the  cases.  Significant  differences  in average daily doses  and concentrations of valproic acid were found in newborns under 1 month of age; overtherapeutic concentrations  in the group of preterm newborns  under 1 month were observed  in 23.5% of the cases versus 9.5% in the group of newborns  of 2-3 months  of age (p=0.07).  Weak inverse  correlation between  age and concentration  of valproic acid was seen in newborns: r=-0.25 for Cmin and r=-0.24 for Cmax. There was no correlation between the dose and concentration of valproic acid, this explains unpredictability of the dose response  in the group of preterm newborns and low rates of achieving therapeutic concentrations.  Conclusion. Specific features of valproic acid pharmacokinetics  in newborns  and children are associated  with specific TDM parameters identified within the study; these  findings show high value of TDM

RESULTS OF THERAPEUTIC DRUG MONITORING COMBINATION THERAPY OF ANTICONVULSANTS IN CLINICAL PRACTICS

Abstract: this paper presents the results of therapeutic drug monitoring (TDM) of anticonvulsants – valproats and carbamazepins. Analysis include 800 patients with epilepsy in clinical practices, who received monotherapy and drug combinations. We determine plasma concentrations in two points: Cmin – before use next dose and Cmax – after next dose; concentration range for valproats – 50-150 mg/l, for carbamazepin – 4-12 mg/l. Plasma concentrations of valproats was statistically low in combination with carbamazepins than in monotherapy: Cmin 44,1±1,4 versus 62.1±2.0 (р<0,001) и Cmax 57.6±1.9 versus 76.5±2.4, without differences in daily doses. The frequency of achievement the therapeutic concentrations of valproats on valproat/carbamazepin combination was 34% versus 67% in monotherapy as result of inducing metabolism valproate acid by carbamazepin. For carbamazepin there was tendency for high frequency of achievement the therapeutic concentrations on combination treatment than on monotherapy – 86% versus 75.9%, but the doses of carbamazepin were also higher in combination therapy. However, plasma concentrations of carbamazepin were statistically higher only in combinations with other anticonvulsants exclude valproats: Cmin 8.0±0.2 versus 6.1±0.16 и Cmax 9.4±0.2 versus 7.3±0.18 (р<0,001) in monotherapy. The frequency of achievement the therapeutic concentrations for valproats and carbamazepin simultaneously in combination therapy was only 28.5%. This demonstrate the level of drug interactions in combination therapy of epilepcy especially with valproats and carbamazepin

THERAPEUTIC DRUG MONITORING OF ANTICONVULSANTS IN CLINICAL PRACTICS

Abstract: his paper presents the results of therapeutic drug monitoring (TDM) of anticonvulsants (valproats and carbamazepins) in 614 patients with epilepsy in clinical practices. 295 patients were treated with different drugs of valproats and 314 patients were treated with different drugs of carbamazepine. The frequency of achievement the therapeutic concentrations on valproat treatment was 66,4%, the average daily dose was 1325,1 mg. The frequency of achievement the therapeutic concentrations on treatment with drug forms with prolong release (Depakin chrono, Convulex retard) was higher, than on drug forms with immediate release. The frequency of subtherapeutic concentrations on valproat treatment was 16,3% and overtherapeutic concentrations – 1%. In doses of valproats less then 500 mg there was no patients with therapeutic concentrations, in doses 1001-1500 mg/day the therapeutic concentrations have 75% patients, in doses higher than 2000 mg/day – there was a risk of overdose. The frequency of achievement the therapeutic concentrations on carbamazepine treatment was 78,6%, the average daily dose was 922,2 mg. The frequency of achievement the therapeutic concentrations on treatment with drug forms with prolong release (Tedretol CR, Finlepsin retard) was higher, than on drug forms with immediate release. The frequency of subtherapeutic concentrations on carbamazepine treatment was 6,3% and overtherapeutic concentrations – 1,25%. When used initial daily doses (less then 600 mg) 64,3% patients have therapeutic concentrations , when used highly doses (high than 600 mg) 87% patients have therapeutic concentrations. In daily doses of carbamazepine higher then 600 mg and 1200 mg the frequency of the overtherapeutic concentrations were 1,3% and 4,1% both by Cmin and Cmax, only by overtherapeutic Cmax – 8,8% and 18,4%