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2.
Acta Clin Croat ; 60(Suppl 3): 16-24, 2021 Dec.
Article in English | MEDLINE | ID: mdl-36405002

ABSTRACT

A prospective study was carried out at the Zagreb University Hospital Centre to evaluate the relationship between epilepsy, antiepileptic drugs (AEDs) and quality of life (QoL) in patients with epilepsy (PE), and its association with depressive symptoms and sexual dysfunction (SD). QoL was assessed by use of the Quality of Life in Epilepsy-31 Inventory (QOLIE-31), SD by the Arizona Sexual Experiences Scale (ASEX), and depressive symptoms by the Hamilton Rating Scale for Depression (HAM-D17). The study included 108 PE (women 63% and men 37% men), mean age 39.54±15.91 years. Focal type epilepsy was diagnosed in 14.8%, generalized type in 35.2%, and both types were present in 40.7% of study patients. Drug-resistant epilepsy (DRE) was present in 44/108 and vagus nerve stimulation (VNS) was implanted in 27/44 patients. The mean response on QOLIE-31 was 62.88±17.21 with no significant differences according to gender, type of epilepsy, and age. A statistically significantly lower QoL was found in the 'Overall QoL' domain (35-55 vs. <35 age group). Patients taking both types of AEDs had a significantly lower QoL compared to those on newer types of AEDs. Higher QoL was associated with less pronounced depressive symptoms (p=0.000). Significant correlations were found between lower QoL and SD (p=0.001). In 27 patients with DRE having undergone VNS, a favorable effect of VNS implantation on the QoL and mood was observed as compared with 18 patients without VNS (p=0.041).


Subject(s)
Epilepsy , Vagus Nerve Stimulation , Male , Humans , Female , Young Adult , Adult , Middle Aged , Quality of Life , Prospective Studies , Epilepsy/complications , Epilepsy/drug therapy , Anticonvulsants/therapeutic use
4.
Br J Clin Pharmacol ; 84(9): 2106-2119, 2018 09.
Article in English | MEDLINE | ID: mdl-29791014

ABSTRACT

AIMS: To investigate the impact of glucuronidation enzyme (UGT1A4*3 142T>G, UGT1A4*2 70C>A, UGT2B7 -161C>T) and transporter (MDR1/ABCB1 1236C>T, ABCG2 421C>A) polymorphisms on steady-state disposition of lamotrigine and on the lamotrigine-valproate interaction. METHODS: Adults with epilepsy on lamotrigine monotherapy (n = 131) or lamotrigine + valproate treatment (n = 74) were genotyped and steady-state lamotrigine and valproate morning troughs were determined as a part of routine therapeutic drug monitoring. RESULTS: No effect of UGT and MDR1/ABCB1 polymorphisms was observed. In the entire cohort, ABCG2 421A allele had no effect however an interaction between the variant allele and valproate was observed: (i) in lamotrigine-only patients, variant allele (vs. wild type homozygosity) was independently (adjustments: age, sex, body mass index, lamotrigine dose, other polymorphisms) associated with mildly lower lamotrigine troughs [geometric means ratio (GMR) = 0.76, 95% confidence interval (CI) 0.59-0.98], whereas in lamotrigine + valproate patients it was associated with higher troughs (GMR = 1.72, 95%CI 1.14-2.62); (ii) valproate cotreatment was overall associated with markedly higher troughs vs. lamotrigine monotherapy (GMR = 3.49, 95%CI 2.73-4.44), but more so in variant allele carriers (GMR = 5.24, 95%CI 3.38-8.15) than in wild type homozygotes (GMR = 2.32, 95%CI 1.89-2.83); (iii) variant allele effects in two treatment subsets and valproate effects in two genotype subsets differed by 2.36-fold (95%CI 1.39-3.67); (iv) increase in lamotrigine troughs associated with increasing valproate troughs was greater in variant allele carriers than in wild type homozygotes, i.e. variant allele effect increased with increasing valproate troughs. CONCLUSION: This study is first to indicate a potentially relevant interaction between ABCG2 421C>A polymorphism and valproate in their effects on lamotrigine disposition.


Subject(s)
ATP Binding Cassette Transporter, Subfamily G, Member 2/genetics , Anticonvulsants/pharmacology , Epilepsy/drug therapy , Lamotrigine/pharmacology , Neoplasm Proteins/genetics , Valproic Acid/pharmacology , ATP Binding Cassette Transporter, Subfamily B/genetics , ATP Binding Cassette Transporter, Subfamily B/metabolism , ATP Binding Cassette Transporter, Subfamily G, Member 2/metabolism , Adolescent , Adult , Aged , Alleles , Anticonvulsants/therapeutic use , Dose-Response Relationship, Drug , Drug Interactions , Drug Therapy, Combination/methods , Epilepsy/genetics , Female , Glucuronosyltransferase/genetics , Glucuronosyltransferase/metabolism , Humans , Lamotrigine/therapeutic use , Male , Middle Aged , Neoplasm Proteins/metabolism , Polymorphism, Single Nucleotide , Prospective Studies , Valproic Acid/therapeutic use , Young Adult
5.
Croat Med J ; 59(1): 13-19, 2018 Feb 28.
Article in English | MEDLINE | ID: mdl-29498493

ABSTRACT

AIM: To estimate the effect size of concomitant antiepileptic therapy on the concentrations of lamotrigine, a drug often prescribed in combination with other antiepileptic drugs (AED), which can act as enzyme inducers or inhibitors. METHODS: A total of 304 patients with epilepsy, aged 18-70 years, were divided into a lamotrigine monotherapy group and groups receiving lamotrigine with AEDs that act as enzyme inducers, enzyme inhibitors, or both. We compared lamotrigine monotherapy serum concentrations with those where lamotrigine was administered with a metabolic inhibitor valproate, metabolic inducers carbamazepine, oxcarbazepine, phenobarbital, phenytoin, or topiramate, and both an inducer and an inhibitor. RESULTS: Comparison of trough lamotrigine monotherapy concentrations and lamotrigine polytherapy concentrations showed an almost similar median concentration in case of drug-inducers, and higher lamotrigine concentration in case of comedication with valproate as an inhibitor. A significant difference was confirmed after dose correction (P<0.001). Significant positive correlations of lamotrigine trough serum concentrations with valproate were observed before and after the dose correction (r=0.480, P<0.001 and r=0.561, P<0.001, respectively). Positive correlations between the dose-corrected lamotrigine trough concentration and carbamazepine (r=0.439; PP<0.001) or monohydroxy metabolite of oxcarbazepine (MHD) (r=0.675; PP<0.001) were also significant. CONCLUSION: Higher valproate levels resulted in higher inhibition potency and higher lamotrigine levels. Increased dose-corrected concentrations of inducers carbamazepine and MHD, after the process of induction was finished, did not lower lamotrigine concentrations. These findings can be of clinical significance for optimal AED dosing.


Subject(s)
Anticonvulsants/administration & dosage , Epilepsy/drug therapy , Triazines/administration & dosage , Adolescent , Adult , Aged , Anticonvulsants/pharmacokinetics , Carbamazepine/administration & dosage , Dose-Response Relationship, Drug , Drug Interactions , Drug Therapy, Combination , Epilepsy/blood , Female , Fructose/administration & dosage , Fructose/analogs & derivatives , Humans , Lamotrigine , Male , Middle Aged , Retrospective Studies , Topiramate , Triazines/pharmacokinetics , Valproic Acid/administration & dosage , Young Adult
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