The effects of co-medications on lamotrigine clearance in Japanese children with epilepsy
Although it has been reported that some antiepileptic drugs have inducing or inhibiting effects on lamotrigine (LTG) clearance, whether they have the same effects in Asian epilepsy patients as in those in other countries has not been clarified, especially in children. The aim of this study was to de...
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| Published in | Brain & development (Tokyo. 1979) Vol. 38; no. 8; pp. 723 - 730 |
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| Main Authors | , , , , , , , , , , , , , , , , , , |
| Format | Journal Article |
| Language | English |
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Netherlands
Elsevier B.V
01.09.2016
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| Online Access | Get full text |
| ISSN | 0387-7604 1872-7131 1872-7131 |
| DOI | 10.1016/j.braindev.2016.03.004 |
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| Abstract | Although it has been reported that some antiepileptic drugs have inducing or inhibiting effects on lamotrigine (LTG) clearance, whether they have the same effects in Asian epilepsy patients as in those in other countries has not been clarified, especially in children. The aim of this study was to determine the effects of co-medications on LTG clearance in Japanese children with epilepsy.
A total of 342 routine serum concentration measurements of LTG in 102 Japanese epilepsy patients under 20years of age were reviewed. The dose-corrected concentration (DCC) of LTG was calculated as [concentration]/[dose/(body weight)], and the DCC of LTG was compared by co-medication. The difference in the DCC of LTG was compared between patients with and without valproic acid (VPA) and between those with and without drugs inducing glucuronic acid conjugation (phenytoin (PHT), carbamazepine (CBZ), and phenobarbital (PB)).
The DCC of LTG was significantly higher in patients on VPA and significantly lower in patients on drugs inducing glucuronic acid conjugation than in patients on LTG monotherapy. The DCC of LTG was significantly higher in patients on CBZ than in patients on PHT or PB. There was no correlation between the DCC of LTG and the concentration of VPA or metabolic inducers within the therapeutic range. Other antiepileptic drugs including clobazam, clonazepam, zonisamide, and levetiracetam had little effect on LTG concentration.
LTG concentration changes dramatically with concomitant antiepileptic drugs in Japanese children, as previously reported from other countries, and special attention is required. Although the dose of LTG should be adjusted when starting or discontinuing VPA or metabolic inducers, no adjustment is needed when changing the dose of VPA or metabolic inducers in the therapeutic range. |
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| AbstractList | Although it has been reported that some antiepileptic drugs have inducing or inhibiting effects on lamotrigine (LTG) clearance, whether they have the same effects in Asian epilepsy patients as in those in other countries has not been clarified, especially in children. The aim of this study was to determine the effects of co-medications on LTG clearance in Japanese children with epilepsy.
A total of 342 routine serum concentration measurements of LTG in 102 Japanese epilepsy patients under 20years of age were reviewed. The dose-corrected concentration (DCC) of LTG was calculated as [concentration]/[dose/(body weight)], and the DCC of LTG was compared by co-medication. The difference in the DCC of LTG was compared between patients with and without valproic acid (VPA) and between those with and without drugs inducing glucuronic acid conjugation (phenytoin (PHT), carbamazepine (CBZ), and phenobarbital (PB)).
The DCC of LTG was significantly higher in patients on VPA and significantly lower in patients on drugs inducing glucuronic acid conjugation than in patients on LTG monotherapy. The DCC of LTG was significantly higher in patients on CBZ than in patients on PHT or PB. There was no correlation between the DCC of LTG and the concentration of VPA or metabolic inducers within the therapeutic range. Other antiepileptic drugs including clobazam, clonazepam, zonisamide, and levetiracetam had little effect on LTG concentration.
LTG concentration changes dramatically with concomitant antiepileptic drugs in Japanese children, as previously reported from other countries, and special attention is required. Although the dose of LTG should be adjusted when starting or discontinuing VPA or metabolic inducers, no adjustment is needed when changing the dose of VPA or metabolic inducers in the therapeutic range. AbstractPurposeAlthough it has been reported that some antiepileptic drugs have inducing or inhibiting effects on lamotrigine (LTG) clearance, whether they have the same effects in Asian epilepsy patients as in those in other countries has not been clarified, especially in children. The aim of this study was to determine the effects of co-medications on LTG clearance in Japanese children with epilepsy. MethodsA total of 342 routine serum concentration measurements of LTG in 102 Japanese epilepsy patients under 20 years of age were reviewed. The dose-corrected concentration (DCC) of LTG was calculated as [concentration]/[dose/(body weight)], and the DCC of LTG was compared by co-medication. The difference in the DCC of LTG was compared between patients with and without valproic acid (VPA) and between those with and without drugs inducing glucuronic acid conjugation (phenytoin (PHT), carbamazepine (CBZ), and phenobarbital (PB)). ResultsThe DCC of LTG was significantly higher in patients on VPA and significantly lower in patients on drugs inducing glucuronic acid conjugation than in patients on LTG monotherapy. The DCC of LTG was significantly higher in patients on CBZ than in patients on PHT or PB. There was no correlation between the DCC of LTG and the concentration of VPA or metabolic inducers within the therapeutic range. Other antiepileptic drugs including clobazam, clonazepam, zonisamide, and levetiracetam had little effect on LTG concentration. ConclusionLTG concentration changes dramatically with concomitant antiepileptic drugs in Japanese children, as previously reported from other countries, and special attention is required. Although the dose of LTG should be adjusted when starting or discontinuing VPA or metabolic inducers, no adjustment is needed when changing the dose of VPA or metabolic inducers in the therapeutic range. Although it has been reported that some antiepileptic drugs have inducing or inhibiting effects on lamotrigine (LTG) clearance, whether they have the same effects in Asian epilepsy patients as in those in other countries has not been clarified, especially in children. The aim of this study was to determine the effects of co-medications on LTG clearance in Japanese children with epilepsy.PURPOSEAlthough it has been reported that some antiepileptic drugs have inducing or inhibiting effects on lamotrigine (LTG) clearance, whether they have the same effects in Asian epilepsy patients as in those in other countries has not been clarified, especially in children. The aim of this study was to determine the effects of co-medications on LTG clearance in Japanese children with epilepsy.A total of 342 routine serum concentration measurements of LTG in 102 Japanese epilepsy patients under 20years of age were reviewed. The dose-corrected concentration (DCC) of LTG was calculated as [concentration]/[dose/(body weight)], and the DCC of LTG was compared by co-medication. The difference in the DCC of LTG was compared between patients with and without valproic acid (VPA) and between those with and without drugs inducing glucuronic acid conjugation (phenytoin (PHT), carbamazepine (CBZ), and phenobarbital (PB)).METHODSA total of 342 routine serum concentration measurements of LTG in 102 Japanese epilepsy patients under 20years of age were reviewed. The dose-corrected concentration (DCC) of LTG was calculated as [concentration]/[dose/(body weight)], and the DCC of LTG was compared by co-medication. The difference in the DCC of LTG was compared between patients with and without valproic acid (VPA) and between those with and without drugs inducing glucuronic acid conjugation (phenytoin (PHT), carbamazepine (CBZ), and phenobarbital (PB)).The DCC of LTG was significantly higher in patients on VPA and significantly lower in patients on drugs inducing glucuronic acid conjugation than in patients on LTG monotherapy. The DCC of LTG was significantly higher in patients on CBZ than in patients on PHT or PB. There was no correlation between the DCC of LTG and the concentration of VPA or metabolic inducers within the therapeutic range. Other antiepileptic drugs including clobazam, clonazepam, zonisamide, and levetiracetam had little effect on LTG concentration.RESULTSThe DCC of LTG was significantly higher in patients on VPA and significantly lower in patients on drugs inducing glucuronic acid conjugation than in patients on LTG monotherapy. The DCC of LTG was significantly higher in patients on CBZ than in patients on PHT or PB. There was no correlation between the DCC of LTG and the concentration of VPA or metabolic inducers within the therapeutic range. Other antiepileptic drugs including clobazam, clonazepam, zonisamide, and levetiracetam had little effect on LTG concentration.LTG concentration changes dramatically with concomitant antiepileptic drugs in Japanese children, as previously reported from other countries, and special attention is required. Although the dose of LTG should be adjusted when starting or discontinuing VPA or metabolic inducers, no adjustment is needed when changing the dose of VPA or metabolic inducers in the therapeutic range.CONCLUSIONLTG concentration changes dramatically with concomitant antiepileptic drugs in Japanese children, as previously reported from other countries, and special attention is required. Although the dose of LTG should be adjusted when starting or discontinuing VPA or metabolic inducers, no adjustment is needed when changing the dose of VPA or metabolic inducers in the therapeutic range. |
| Author | Takeuchi, Tomoya Abe, Shinpei Ishihara, Naoko Okumura, Akihisa Kurahashi, Naoko Natsume, Jun Kidokoro, Hiroyuki Yamada, Keitaro Yamamoto, Hiroyuki Kurahashi, Hirokazu Itomi, Kazuya Ito, Yuji Azuma, Yoshiteru Tsuji, Takeshi Kojima, Seiji Maruyama, Koichi Negoro, Tamiko Suzuki, Motomasa Watanabe, Kazuyoshi |
| Author_xml | – sequence: 1 givenname: Tomoya orcidid: 0000-0002-6006-5258 surname: Takeuchi fullname: Takeuchi, Tomoya email: tmtakeuchi-nagoya@umin.net organization: Department of Pediatrics, Nagoya University Graduate School of Medicine, Nagoya, Japan – sequence: 2 givenname: Jun surname: Natsume fullname: Natsume, Jun organization: Department of Pediatrics, Nagoya University Graduate School of Medicine, Nagoya, Japan – sequence: 3 givenname: Hiroyuki surname: Kidokoro fullname: Kidokoro, Hiroyuki organization: Department of Pediatrics, Nagoya University Graduate School of Medicine, Nagoya, Japan – sequence: 4 givenname: Naoko surname: Ishihara fullname: Ishihara, Naoko organization: Department of Pediatrics, Nagoya University Graduate School of Medicine, Nagoya, Japan – sequence: 5 givenname: Hiroyuki surname: Yamamoto fullname: Yamamoto, Hiroyuki organization: Department of Pediatrics, Nagoya University Graduate School of Medicine, Nagoya, Japan – sequence: 6 givenname: Yoshiteru surname: Azuma fullname: Azuma, Yoshiteru organization: Department of Pediatrics, Nagoya University Graduate School of Medicine, Nagoya, Japan – sequence: 7 givenname: Yuji surname: Ito fullname: Ito, Yuji organization: Department of Pediatrics, Nagoya University Graduate School of Medicine, Nagoya, Japan – sequence: 8 givenname: Naoko surname: Kurahashi fullname: Kurahashi, Naoko organization: Department of Pediatric Neurology, Central Hospital, Aichi Human Service Center, Kasugai, Japan – sequence: 9 givenname: Takeshi surname: Tsuji fullname: Tsuji, Takeshi organization: Department of Pediatrics, Okazaki City Hospital, Okazaki, Japan – sequence: 10 givenname: Motomasa surname: Suzuki fullname: Suzuki, Motomasa organization: Aichi Children’s Health and Medical Center, Ohbu, Japan – sequence: 11 givenname: Kazuya surname: Itomi fullname: Itomi, Kazuya organization: Aichi Children’s Health and Medical Center, Ohbu, Japan – sequence: 12 givenname: Keitaro surname: Yamada fullname: Yamada, Keitaro organization: Department of Pediatric Neurology, Central Hospital, Aichi Human Service Center, Kasugai, Japan – sequence: 13 givenname: Hirokazu surname: Kurahashi fullname: Kurahashi, Hirokazu organization: Department of Pediatric Neurology, Central Hospital, Aichi Human Service Center, Kasugai, Japan – sequence: 14 givenname: Shinpei surname: Abe fullname: Abe, Shinpei organization: Department of Pediatrics, Juntendo University Hospital, Tokyo, Japan – sequence: 15 givenname: Akihisa surname: Okumura fullname: Okumura, Akihisa organization: Department of Pediatrics, Juntendo University Hospital, Tokyo, Japan – sequence: 16 givenname: Koichi surname: Maruyama fullname: Maruyama, Koichi organization: Department of Pediatric Neurology, Central Hospital, Aichi Human Service Center, Kasugai, Japan – sequence: 17 givenname: Tamiko surname: Negoro fullname: Negoro, Tamiko organization: Department of Pediatrics, Nagoya University Graduate School of Medicine, Nagoya, Japan – sequence: 18 givenname: Kazuyoshi surname: Watanabe fullname: Watanabe, Kazuyoshi organization: Department of Pediatrics, Nagoya University Graduate School of Medicine, Nagoya, Japan – sequence: 19 givenname: Seiji surname: Kojima fullname: Kojima, Seiji organization: Department of Pediatrics, Nagoya University Graduate School of Medicine, Nagoya, Japan |
| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/27033151$$D View this record in MEDLINE/PubMed |
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| CitedBy_id | crossref_primary_10_1080_17425255_2016_1203900 crossref_primary_10_1016_j_jpba_2017_11_042 crossref_primary_10_1016_j_talanta_2017_05_018 crossref_primary_10_1016_j_yebeh_2019_04_007 crossref_primary_10_1371_journal_pone_0307377 |
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| Keywords | Co-medication Drug interaction Drug concentration Child Epilepsy Lamotrigine |
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| Snippet | Although it has been reported that some antiepileptic drugs have inducing or inhibiting effects on lamotrigine (LTG) clearance, whether they have the same... AbstractPurposeAlthough it has been reported that some antiepileptic drugs have inducing or inhibiting effects on lamotrigine (LTG) clearance, whether they... |
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| SubjectTerms | Adolescent Anticonvulsants - administration & dosage Anticonvulsants - pharmacokinetics Benzodiazepines - administration & dosage Carbamazepine - administration & dosage Child Child, Preschool Clonazepam - administration & dosage Co-medication Drug concentration Drug interaction Drug Interactions Drug Therapy, Combination Epilepsy Epilepsy - blood Epilepsy - drug therapy Female Humans Infant Infant, Newborn Isoxazoles - administration & dosage Japan Lamotrigine Male Neurology Phenobarbital - administration & dosage Phenytoin - administration & dosage Piracetam - administration & dosage Piracetam - analogs & derivatives Triazines - administration & dosage Triazines - pharmacokinetics Valproic Acid - administration & dosage Young Adult |
| Title | The effects of co-medications on lamotrigine clearance in Japanese children with epilepsy |
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