Influence of age and co-medication on the steady-state pharmacokinetics of valproic acid in Tunisian patients with epilepsy.
Identifieur interne : 000378 ( Main/Exploration ); précédent : 000377; suivant : 000379Influence of age and co-medication on the steady-state pharmacokinetics of valproic acid in Tunisian patients with epilepsy.
Auteurs : L. Ben Mahmoud [Tunisie] ; A. Hakim [Tunisie] ; H. Ghozzi [Tunisie] ; R. Atheymen [Tunisie] ; Z. Sahnoun [Tunisie] ; K. Zeghal [Tunisie]Source :
- Revue neurologique [ 0035-3787 ] ; 2017.
Descripteurs français
- KwdFr :
- Acide valproïque (administration et posologie), Acide valproïque (pharmacocinétique), Acide valproïque (sang), Activateurs d'enzymes (administration et posologie), Activateurs d'enzymes (pharmacocinétique), Activateurs d'enzymes (sang), Adolescent (MeSH), Adulte (MeSH), Adulte d'âge moyen (MeSH), Anticonvulsivants (administration et posologie), Anticonvulsivants (pharmacocinétique), Anticonvulsivants (sang), Association de médicaments (MeSH), Enfant (MeSH), Enfant d'âge préscolaire (MeSH), Facteurs âges (MeSH), Femelle (MeSH), Humains (MeSH), Interactions médicamenteuses (MeSH), Jeune adulte (MeSH), Mâle (MeSH), Polypharmacie (MeSH), Surveillance des médicaments (MeSH), Épilepsie (métabolisme), Épilepsie (traitement médicamenteux), Études rétrospectives (MeSH).
- MESH :
- administration et posologie : Acide valproïque, Activateurs d'enzymes, Anticonvulsivants.
- métabolisme : Épilepsie.
- pharmacocinétique : Acide valproïque, Activateurs d'enzymes, Anticonvulsivants.
- sang : Acide valproïque, Activateurs d'enzymes, Anticonvulsivants.
- traitement médicamenteux : Épilepsie.
- Adolescent, Adulte, Adulte d'âge moyen, Association de médicaments, Enfant, Enfant d'âge préscolaire, Facteurs âges, Femelle, Humains, Interactions médicamenteuses, Jeune adulte, Mâle, Polypharmacie, Surveillance des médicaments, Études rétrospectives.
English descriptors
- KwdEn :
- Adolescent (MeSH), Adult (MeSH), Age Factors (MeSH), Anticonvulsants (administration & dosage), Anticonvulsants (blood), Anticonvulsants (pharmacokinetics), Child (MeSH), Child, Preschool (MeSH), Drug Interactions (MeSH), Drug Monitoring (MeSH), Drug Therapy, Combination (MeSH), Enzyme Activators (administration & dosage), Enzyme Activators (blood), Enzyme Activators (pharmacokinetics), Epilepsy (drug therapy), Epilepsy (metabolism), Female (MeSH), Humans (MeSH), Male (MeSH), Middle Aged (MeSH), Polypharmacy (MeSH), Retrospective Studies (MeSH), Valproic Acid (administration & dosage), Valproic Acid (blood), Valproic Acid (pharmacokinetics), Young Adult (MeSH).
- MESH :
- chemical , administration & dosage : Anticonvulsants, Enzyme Activators, Valproic Acid.
- chemical , blood : Anticonvulsants, Enzyme Activators, Valproic Acid.
- chemical , pharmacokinetics : Anticonvulsants, Enzyme Activators, Valproic Acid.
- drug therapy : Epilepsy.
- metabolism : Epilepsy.
- Adolescent, Adult, Age Factors, Child, Child, Preschool, Drug Interactions, Drug Monitoring, Drug Therapy, Combination, Female, Humans, Male, Middle Aged, Polypharmacy, Retrospective Studies, Young Adult.
Abstract
AIM
Valproic acid (VPA) is a widely prescribed broad-spectrum antiepileptic drug. However, the use of VPA is complicated in clinical practice by its remarkably wide variability of pharmacokinetics. The objective of this study was to investigate the effects of demographic factors and associated therapies on steady-state plasma VPA concentrations in patients with epilepsy.
METHODS
This retrospective cohort study was carried out using the routine therapeutic drug monitoring (TDM) database. Stepwise logistic regression analysis was used to compare serum VPA levels in 78 epilepsy patients treated with VPA in association with at least one other drug that could have interacted with CYP2C9, CYP2C19 or UGT enzymes.
RESULTS
The frequency of subtherapeutic serum VPA levels was significantly increased with younger age (P<0.02), the number of co-medications (P<0.007) and use of enzyme-inducing co-medications (P<0.02). No significant correlations between VPA dose and trough plasma concentrations were found, as the latter did not increase in proportion to the dose.
CONCLUSION
Routine monitoring of VPA serum levels would be extremely useful in epilepsy patients in the pediatric age group and in those who require associated enzyme-inducing medications.
DOI: 10.1016/j.neurol.2017.02.004
PubMed: 28320517
Affiliations:
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Ben Mahmoud</name><affiliation wicri:level="1"><nlm:affiliation>University of Sfax, Faculty of Medicine, Pharmacology Department, Bd Majida Boulila, Sfax 3029, Tunisia. Electronic address: benmahmoud_lobna@medecinesfax.org.</nlm:affiliation><country xml:lang="fr">Tunisie</country><wicri:regionArea>University of Sfax, Faculty of Medicine, Pharmacology Department, Bd Majida Boulila, Sfax 3029</wicri:regionArea><wicri:noRegion>Sfax 3029</wicri:noRegion></affiliation></author><author><name sortKey="Hakim, A" sort="Hakim, A" uniqKey="Hakim A" first="A" last="Hakim">A. Hakim</name><affiliation wicri:level="1"><nlm:affiliation>University of Sfax, Faculty of Medicine, Pharmacology Department, Bd Majida Boulila, Sfax 3029, Tunisia.</nlm:affiliation><country xml:lang="fr">Tunisie</country><wicri:regionArea>University of Sfax, Faculty of Medicine, Pharmacology Department, Bd Majida Boulila, Sfax 3029</wicri:regionArea><wicri:noRegion>Sfax 3029</wicri:noRegion></affiliation></author><author><name sortKey="Ghozzi, H" sort="Ghozzi, H" uniqKey="Ghozzi H" first="H" last="Ghozzi">H. Ghozzi</name><affiliation wicri:level="1"><nlm:affiliation>University of Sfax, Faculty of Medicine, Pharmacology Department, Bd Majida Boulila, Sfax 3029, Tunisia.</nlm:affiliation><country xml:lang="fr">Tunisie</country><wicri:regionArea>University of Sfax, Faculty of Medicine, Pharmacology Department, Bd Majida Boulila, Sfax 3029</wicri:regionArea><wicri:noRegion>Sfax 3029</wicri:noRegion></affiliation></author><author><name sortKey="Atheymen, R" sort="Atheymen, R" uniqKey="Atheymen R" first="R" last="Atheymen">R. Atheymen</name><affiliation wicri:level="1"><nlm:affiliation>University of Sfax, Faculty of Medicine, Pharmacology Department, Bd Majida Boulila, Sfax 3029, Tunisia.</nlm:affiliation><country xml:lang="fr">Tunisie</country><wicri:regionArea>University of Sfax, Faculty of Medicine, Pharmacology Department, Bd Majida Boulila, Sfax 3029</wicri:regionArea><wicri:noRegion>Sfax 3029</wicri:noRegion></affiliation></author><author><name sortKey="Sahnoun, Z" sort="Sahnoun, Z" uniqKey="Sahnoun Z" first="Z" last="Sahnoun">Z. Sahnoun</name><affiliation wicri:level="1"><nlm:affiliation>University of Sfax, Faculty of Medicine, Pharmacology Department, Bd Majida Boulila, Sfax 3029, Tunisia.</nlm:affiliation><country xml:lang="fr">Tunisie</country><wicri:regionArea>University of Sfax, Faculty of Medicine, Pharmacology Department, Bd Majida Boulila, Sfax 3029</wicri:regionArea><wicri:noRegion>Sfax 3029</wicri:noRegion></affiliation></author><author><name sortKey="Zeghal, K" sort="Zeghal, K" uniqKey="Zeghal K" first="K" last="Zeghal">K. Zeghal</name><affiliation wicri:level="1"><nlm:affiliation>University of Sfax, Faculty of Medicine, Pharmacology Department, Bd Majida Boulila, Sfax 3029, Tunisia.</nlm:affiliation><country xml:lang="fr">Tunisie</country><wicri:regionArea>University of Sfax, Faculty of Medicine, Pharmacology Department, Bd Majida Boulila, Sfax 3029</wicri:regionArea><wicri:noRegion>Sfax 3029</wicri:noRegion></affiliation></author></analytic><series><title level="j">Revue neurologique</title><idno type="ISSN">0035-3787</idno><imprint><date when="2017" type="published">2017</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Adolescent (MeSH)</term><term>Adult (MeSH)</term><term>Age Factors (MeSH)</term><term>Anticonvulsants (administration & dosage)</term><term>Anticonvulsants (blood)</term><term>Anticonvulsants (pharmacokinetics)</term><term>Child (MeSH)</term><term>Child, Preschool (MeSH)</term><term>Drug Interactions (MeSH)</term><term>Drug Monitoring (MeSH)</term><term>Drug Therapy, Combination (MeSH)</term><term>Enzyme Activators (administration & dosage)</term><term>Enzyme Activators (blood)</term><term>Enzyme Activators (pharmacokinetics)</term><term>Epilepsy (drug therapy)</term><term>Epilepsy (metabolism)</term><term>Female (MeSH)</term><term>Humans (MeSH)</term><term>Male (MeSH)</term><term>Middle Aged (MeSH)</term><term>Polypharmacy (MeSH)</term><term>Retrospective Studies (MeSH)</term><term>Valproic Acid (administration & dosage)</term><term>Valproic Acid (blood)</term><term>Valproic Acid (pharmacokinetics)</term><term>Young Adult (MeSH)</term></keywords><keywords scheme="KwdFr" xml:lang="fr"><term>Acide valproïque (administration et posologie)</term><term>Acide valproïque (pharmacocinétique)</term><term>Acide valproïque (sang)</term><term>Activateurs d'enzymes (administration et posologie)</term><term>Activateurs d'enzymes (pharmacocinétique)</term><term>Activateurs d'enzymes (sang)</term><term>Adolescent (MeSH)</term><term>Adulte (MeSH)</term><term>Adulte d'âge moyen (MeSH)</term><term>Anticonvulsivants (administration et posologie)</term><term>Anticonvulsivants (pharmacocinétique)</term><term>Anticonvulsivants (sang)</term><term>Association de médicaments (MeSH)</term><term>Enfant (MeSH)</term><term>Enfant d'âge préscolaire (MeSH)</term><term>Facteurs âges (MeSH)</term><term>Femelle (MeSH)</term><term>Humains (MeSH)</term><term>Interactions médicamenteuses (MeSH)</term><term>Jeune adulte (MeSH)</term><term>Mâle (MeSH)</term><term>Polypharmacie (MeSH)</term><term>Surveillance des médicaments (MeSH)</term><term>Épilepsie (métabolisme)</term><term>Épilepsie (traitement médicamenteux)</term><term>Études rétrospectives (MeSH)</term></keywords><keywords scheme="MESH" type="chemical" qualifier="administration & dosage" xml:lang="en"><term>Anticonvulsants</term><term>Enzyme Activators</term><term>Valproic Acid</term></keywords><keywords scheme="MESH" type="chemical" qualifier="blood" xml:lang="en"><term>Anticonvulsants</term><term>Enzyme Activators</term><term>Valproic Acid</term></keywords><keywords scheme="MESH" type="chemical" qualifier="pharmacokinetics" xml:lang="en"><term>Anticonvulsants</term><term>Enzyme Activators</term><term>Valproic Acid</term></keywords><keywords scheme="MESH" qualifier="administration et posologie" xml:lang="fr"><term>Acide valproïque</term><term>Activateurs d'enzymes</term><term>Anticonvulsivants</term></keywords><keywords scheme="MESH" qualifier="drug therapy" xml:lang="en"><term>Epilepsy</term></keywords><keywords scheme="MESH" qualifier="metabolism" xml:lang="en"><term>Epilepsy</term></keywords><keywords scheme="MESH" qualifier="métabolisme" xml:lang="fr"><term>Épilepsie</term></keywords><keywords scheme="MESH" qualifier="pharmacocinétique" xml:lang="fr"><term>Acide valproïque</term><term>Activateurs d'enzymes</term><term>Anticonvulsivants</term></keywords><keywords scheme="MESH" qualifier="sang" xml:lang="fr"><term>Acide valproïque</term><term>Activateurs d'enzymes</term><term>Anticonvulsivants</term></keywords><keywords scheme="MESH" qualifier="traitement médicamenteux" xml:lang="fr"><term>Épilepsie</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Adolescent</term><term>Adult</term><term>Age Factors</term><term>Child</term><term>Child, Preschool</term><term>Drug Interactions</term><term>Drug Monitoring</term><term>Drug Therapy, Combination</term><term>Female</term><term>Humans</term><term>Male</term><term>Middle Aged</term><term>Polypharmacy</term><term>Retrospective Studies</term><term>Young Adult</term></keywords><keywords scheme="MESH" xml:lang="fr"><term>Adolescent</term><term>Adulte</term><term>Adulte d'âge moyen</term><term>Association de médicaments</term><term>Enfant</term><term>Enfant d'âge préscolaire</term><term>Facteurs âges</term><term>Femelle</term><term>Humains</term><term>Interactions médicamenteuses</term><term>Jeune adulte</term><term>Mâle</term><term>Polypharmacie</term><term>Surveillance des médicaments</term><term>Études rétrospectives</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p><b>AIM</b></p><p>Valproic acid (VPA) is a widely prescribed broad-spectrum antiepileptic drug. However, the use of VPA is complicated in clinical practice by its remarkably wide variability of pharmacokinetics. The objective of this study was to investigate the effects of demographic factors and associated therapies on steady-state plasma VPA concentrations in patients with epilepsy.</p></div><div type="abstract" xml:lang="en"><p><b>METHODS</b></p><p>This retrospective cohort study was carried out using the routine therapeutic drug monitoring (TDM) database. Stepwise logistic regression analysis was used to compare serum VPA levels in 78 epilepsy patients treated with VPA in association with at least one other drug that could have interacted with CYP2C9, CYP2C19 or UGT enzymes.</p></div><div type="abstract" xml:lang="en"><p><b>RESULTS</b></p><p>The frequency of subtherapeutic serum VPA levels was significantly increased with younger age (P<0.02), the number of co-medications (P<0.007) and use of enzyme-inducing co-medications (P<0.02). No significant correlations between VPA dose and trough plasma concentrations were found, as the latter did not increase in proportion to the dose.</p></div><div type="abstract" xml:lang="en"><p><b>CONCLUSION</b></p><p>Routine monitoring of VPA serum levels would be extremely useful in epilepsy patients in the pediatric age group and in those who require associated enzyme-inducing medications.</p></div></front></TEI><affiliations><list><country><li>Tunisie</li></country></list><tree><country name="Tunisie"><noRegion><name sortKey="Ben Mahmoud, L" sort="Ben Mahmoud, L" uniqKey="Ben Mahmoud L" first="L" last="Ben Mahmoud">L. Ben Mahmoud</name></noRegion><name sortKey="Atheymen, R" sort="Atheymen, R" uniqKey="Atheymen R" first="R" last="Atheymen">R. Atheymen</name><name sortKey="Ghozzi, H" sort="Ghozzi, H" uniqKey="Ghozzi H" first="H" last="Ghozzi">H. Ghozzi</name><name sortKey="Hakim, A" sort="Hakim, A" uniqKey="Hakim A" first="A" last="Hakim">A. Hakim</name><name sortKey="Sahnoun, Z" sort="Sahnoun, Z" uniqKey="Sahnoun Z" first="Z" last="Sahnoun">Z. Sahnoun</name><name sortKey="Zeghal, K" sort="Zeghal, K" uniqKey="Zeghal K" first="K" last="Zeghal">K. Zeghal</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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