THERAPEUTIC DRUG MONITORING OF ANTICONVULSANTS IN CHILDREN IN CLINICAL PRACTICE
https://doi.org/10.17749/2077-8333.2017.9.1.026-034
Abstract
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.
About the Authors
M. V. LeonovaRussian Federation
Leonova Marina Vasilievna – MD, professor, chief of the Department of Clinical Pharmacology.
Ostrovityanova St., Moscow, 117997, Tel. +7(495)434-03-29
M. A. Ivzhits
Russian Federation
Ivzhits Marina Alexandrovna – assistant of the Department of General and Clinical Pharmacology, medical faculty at PFU.
6 Miclucho-Maclaya St., Moscow, 117198, Tel. +7(495)787-38-27
I. F. Tischenkova
Russian Federation
Tishchenkova Irina Fedorovna – PhD, head of the laboratory, Department of Clinical Pharmacology.
1 Ostrovityanova St., Moscow, 117997, Tel. +7(495)434-03-29
L. L. Shteinberg
Russian Federation
Shteinberg Ludmila Lvovna – PhD, physician, Clinical Research Center.
44 Karamyshevskaya nab., Moscow, 123423, Tel. +7(499)346-21-15, EXT.137 or 121
References
1. Patsalos P. N., Berry D. J., Bourgeois B. F. et al. Antiepileptic drugs-best practice guidelines for therapeutic drug monitoring: a position paper by the subcommission on therapeutic drug monitoring, ILAE Commission on Therapeutic Strategies. Epilepsia. 2008; 49 (7): 1239-76.
2. Johannessen S. I., L andmark C. J. Value of therapeutic drug monitoring in epi-lepsy. Exper t Rev Neurother. 2008; 8 (6): 929 -39.
3. Milsap R. L., Jusko W. J. Pharmacokinetics in the Infant. Environ Health Perspect. 1994; 102 (11): 107-110.
4. Morselli P. L., Franco-Morselli R., Bossi L. Clinical Pharmacokinetics in New-borns and Infants: Age-related Differences and Therapeutic Implications. Clinical Pharmacokinetics.1980; 5: 485-527.
5. Gilmall J. T. Therapeutic Drug Monitoring in the Neonate and Paediatric Age Group: Problems and Clinical Pharmacokinetic Implications. Clin Pharmacokinet. 1990; 19: 1-10.
6. Walson P. D. Role of Therapeutic Drug Monitoring (TDM) in Pediatric AntiConvulsant Drug Dosing. Brain Dev. 1994; 16 (1): 23-26.
7. Aldaz A., Ferriols R., Aumente D. et al. Pharmacokinetic Monitoring of Antiepileptic Drugs. Farm Hosp. 2011; 35: 326-39.
8. Ghodke-Puranik Y., Thorn C. F., Lamba J. K. et al. Valproic acid pathway: pharmacokinetics and pharmacodynamics. Pharmacogenetics and genomics. 2013; 23 (4): 236-41.
9. Neels H. M., Sierens A. C., Naelaerts K. et al. Therapeutic drug monitoring of old and newer antiepileptic Lab Med. 2004; 42 (11): 1228-55.
10. Warner A., Privitera M., David B. Standards of laboratory practice: antiepilep-tic drug monitoring. Clinical Chemistry. 1998; 44 (5): 1085-95.
11. Gusev E. I., Belousov Yu. B., Gekht A. B., Bondareva I. B., Sokolov A. V., Tishchenkova I. F. Treatment of epilepsy: rational dosing of anticonvulsants [Lechenie epilepsii: ratsional’noe dozirovanie antikonvul’-santov (in russian)]. SPb. 2000; 203 s.
12. Belousov Yu. B., Leonova M. V., Shteinberg L. L., Tishchenkova I. F., Soko-lov A. V. Epilepsiya i paroksizmal’nye sostoyaniya / Epilepsy and paroxysmal conditions. 2013; 5 (3): 6-16.
13. Evtushenko S. K., Ivanova N. Yu., Omel’yanenko A. A., Evtushenko I. S. Mezhdunarodnyi nevrologicheskii zhurnal. 2008; 5 (21): 15-21.
Review
For citations:
Leonova M.V., Ivzhits M.A., Tischenkova I.F., Shteinberg L.L. THERAPEUTIC DRUG MONITORING OF ANTICONVULSANTS IN CHILDREN IN CLINICAL PRACTICE. Epilepsy and paroxysmal conditions. 2017;9(1):26-34. (In Russ.) https://doi.org/10.17749/2077-8333.2017.9.1.026-034

This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License.