INTRODUCTION: Topamax (topiramate) is a drug used in the treatment of epilepsy or migraine. Its use may rarely be associated with the occurrence of secondary angle-closure glaucoma due to supraciliary effusion. Although the ocular finding resembles primary angle-closure glaucoma, bilateral infliction should always raise the suspicion that it is drug-induced glaucoma. CASE REPORT: The authors present a case of a 51-year-old patient on Topamax therapy with sudden vertigo, headache and blurred vision. Ophthalmic examination revealed bilateral angle-closure glaucoma, which was initially treated in the classical manner by administration of local antiglaucoma drugs and pilocarpine, followed by administration of osmotically active substances and laser iridotomy. Only the subsequent discontinuation of Topamax and the use of local cycloplegics and corticosteroids led to the release of the anterior segment angle closure and normalization of intraocular pressure. CONCLUSION: The indicating physician and ophthalmologist must be aware of the possible side effects of Topamax therapy to determine the correct diagnosis and to administer treatment appropriately.

• Klíčová slova
• Epilepsy, Migraine, acute myopia, angle-closure glaucoma, epilepsy, migraine, topamax, topiramate,
• MeSH
• fruktosa škodlivé účinky   MeSH
• glaukom s uzavřeným úhlem * chemicky indukované   diagnóza   MeSH
• lidé středního věku MeSH
• lidé MeSH
• nitrooční tlak MeSH
• tonometrie oční MeSH
• topiramat škodlivé účinky   MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• kazuistiky MeSH
• Názvy látek
• fruktosa MeSH
• topiramat MeSH

INTRODUCTION: The aim of this study is to present a case of 44 years old woman with topiramate induced metabolic acidosis and kidney stones. MATERIALS AND METHODS: The laboratory features of topiramate caused renal tubular acidosis in blood and urine during topiramate treatment, with correction of metabolic acidosis by potassium citrate, and after topiramate withdrawal are presented. Differential diagnosis of all possible causes of metabolic acidosis is discussed. RESULTS: The results revealed negative base excess in extracellular fluid of - 9.2 mmol/L, low serum HCO3- concentration (18.6 mmol/L), trend to alkaline urine (pH 6.39) and low urine citrate concentration (0.3 mmol/24h). After topiramate withdrawal, all parameters of the internal environment normalized. CONCLUSIONS: This study has shown that long-term topiramate administration could induce metabolic acidosis and consequently urholithiasis. Thus, we could recommend testing blood acid base balance, urinary pH and citrates in patients taking topiramate and suffering from kidney stones.

• Klíčová slova
• acidosis, glomerular filtration rate, renal tubular acidosis, topiramate, urolithiasis,
• MeSH
• acidóza chemicky indukované   MeSH
• antikonvulziva škodlivé účinky   MeSH
• dospělí MeSH
• fruktosa škodlivé účinky   analogy a deriváty   MeSH
• ledvinové kameny chemicky indukované   MeSH
• lidé MeSH
• migréna prevence a kontrola   MeSH
• nenasazení léčby MeSH
• topiramat MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• kazuistiky MeSH
• Názvy látek
• antikonvulziva MeSH
• fruktosa MeSH
• topiramat MeSH

OBJECTIVE: To determine transplacental passage of topiramate and its transport to colostrum, mature maternal milk and breastfed infants, we examined data from 27 women treated with topiramate from 2004 to 2020. METHODS: In this cohort study, maternal serum, umbilical cord serum, milk and infant serum levels were measured by gas chromatography in the delivery subgroup, the colostrum subgroup (3-4 days postpartum) and the mature milk subgroup (7-30 days postpartum). Paired umbilical cord serum, maternal serum, breastfed infant serum, and milk levels were used to assess the ratios of umbilical cord/maternal serum, milk/maternal serum and infant/maternal serum levels. RESULTS: Topiramate levels varied from 1.0 to 7.1 mg/L in maternal serum and from 0.8 to 6.2 mg/L in umbilical cord serum, and the mean umbilical cord/maternal serum ratio was 0.93 ± 0.11. At 3-4 days after delivery, topiramate concentrations were 1.4-8.4 mg/L in maternal serum, 1.5-8.6 mg/L in milk and 0.3-4.4 mg/L in infant serum. The mean milk/maternal serum ratio was 0.99 ± 0.45, and the mean infant/maternal serum ratio was 0.25 ± 0.15. At 7-30 days after delivery, maternal serum levels varied from 1.9 to 9.7 mg/L, milk levels ranged from 2.3 to 10.6 mg/L and infant serum levels ranged from 0.3 to 6.5 mg/L. The mean milk/maternal serum ratio was 1.07 ± 0.31, and the mean infant/maternal serum ratio was 0.51 ± 0.27. CONCLUSIONS: We extended information about free transplacental passage of topiramate and its extensive transport to maternal milk with lower serum concentrations in breastfed infants in the largest group of patients ever reported to our knowledge. DATA AVAILABILITY STATEMENT: Authors declare that take full responsibility for the data, the analyses and interpretation, and the conduct of the research; that they have full access to all of the data; and that they have the right to publish all data. Authors were not participations in industry-sponsored research and corporate activities for evaluation of a manuscript.

• Klíčová slova
• Breastfeeding, Delivery, Therapeutic drug monitoring, Topiramate,
• MeSH
• antikonvulziva aplikace a dávkování   analýza   metabolismus   MeSH
• dospělí MeSH
• kohortové studie MeSH
• kojení MeSH
• laktace účinky léků   metabolismus   MeSH
• lidé MeSH
• mateřské mléko účinky léků   metabolismus   MeSH
• mladý dospělý MeSH
• monitorování léčiv metody   MeSH
• novorozenec MeSH
• topiramat aplikace a dávkování   analýza   metabolismus   MeSH
• vedení porodu metody   MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• novorozenec MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• antikonvulziva MeSH
• topiramat MeSH

AIMS: The Norwegian Association for Clinical Pharmacology in their National Guidelines decreased the therapeutic range (TR) of topiramate (TPM) from 5-20 mg/L to 2-10 mg/L. The objective of this study is to ascertain which TR produces better clinical outcomes. METHODS: The data sources were request forms for routine therapeutic drug monitoring (TDM) of TPM. Concentration dependent adverse drug reactions (ADRs) were evaluated in 1721 samples taken pre-dose. Seizure frequency analysis was performed in 294 samples of monotherapy. Statistical analysis was performed using Prism 5.0, GraphPad Instatt: One-way ANOVA with Bonferroni correction for median plasma level (PL) and χ2 -test with Bonferroni correction for seizure frequency and for distribution of PL according to TR 5-20 mg/L and intervals <2, 2-5, 5-10, 10-20, >20 mg/L. RESULTS: Better seizure control was found in children both in the whole cohort (without seizure 49% vs 37% adults), as well as in monotherapy (56% vs 44%), in children with PL 5-20 mg/L vs <5 mg/L (65% vs 44%) and in children with PL 5-10 mg/L vs <2 mg/L (63 vs 14%). PL in seizure-free patients did not differ from those with seizure. Seizure control was poorer in the period 2003-2005 compared to 2006-2011. ADRs reported in 38 samples (2.8%) were not related to PL. CONCLUSIONS: Change of TR is not recommended.

• Klíčová slova
• adverse drug reaction, seizure frequency, therapeutic drug monitoring, topiramate,
• MeSH
• antikonvulziva škodlivé účinky   MeSH
• dítě MeSH
• dospělí MeSH
• epilepsie * farmakoterapie   MeSH
• fruktosa škodlivé účinky   MeSH
• lidé MeSH
• nežádoucí účinky léčiv * MeSH
• topiramat škodlivé účinky   MeSH
• záchvaty chemicky indukované   farmakoterapie   MeSH
• Check Tag
• dítě MeSH
• dospělí MeSH
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• antikonvulziva MeSH
• fruktosa MeSH
• topiramat MeSH

BACKGROUND: Topiramate (TPM) decreases cytokine release and generation of reactive oxygen species (ROS). Cytokine and endothelin-1 (ET-1) secretion and ROS formation play an important role in ischemia-reperfusion (I/R) injury. We aimed to evaluate whether TPM prevents damage occurring in lung tissue during I/R. MATERIALS AND METHODS: A total of 27 Wistar albino rats were divided into three groups of nine. To the I/R group, two hours of ischemia via infrarenal abdominal aorta cross-ligation and then two hours of reperfusion process were applied. TPM (100 mg/kg/day) orally for seven days was administered in the TPM treatment group. After the last dose of TPM treatment, respectively, two hours of ischemia and two hours of reperfusion were applied in this group. RESULTS: Tumor necrosis factor-alpha (TNF-α) (p < 0.05), malondialdehyde (MDA) (p < 0.05), myeloperoxidase (MPO) (p < 0.05) and ET-1 (p < 0.05) levels of TPM treatment group's lung tissue were significantly lower than for the I/R group. Caspase-3 and histopathological damage were rather lower than that of the I/R group. CONCLUSIONS: During I/R, lung damage occurs due to excessive TNF-α and ET-1 release and ROS generation. TPM could well reduce development of lung damage by decreasing cytokine and ET-1 release and levels of ROS produced.

• Klíčová slova
• endothelin-1, ischemia-reperfusion, lung injury, topiramate, tumor necrosis factor-alpha,
• MeSH
• aorta abdominalis MeSH
• biologické markery krev   MeSH
• kaspasa 3 krev   MeSH
• krysa rodu Rattus MeSH
• ligace MeSH
• malondialdehyd krev   MeSH
• peroxidasa krev   MeSH
• poškození plic farmakoterapie   MeSH
• potkani Wistar MeSH
• reperfuzní poškození farmakoterapie   MeSH
• TNF-alfa krev   MeSH
• topiramat farmakologie   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• biologické markery MeSH
• kaspasa 3 MeSH
• malondialdehyd MeSH
• peroxidasa MeSH
• TNF-alfa MeSH
• topiramat MeSH

There is only limited data concerning the effect of the newer antiepileptic drugs on bone. The objective of this study was to determine the effect of topiramate (TPM) and lamotrigine (LTG) monotherapy on bone mineral density (BMD), mineral content (BMC), bone markers, body composition and bone mechanical strength in the orchidectomized (ORX) rat model. 24 orchidectomized Wistar rats were divided into control and test groups, 8 rats in each group. The control rats received standard laboratory diet (SLD) while rats in the test group were fed with SLD enriched with LTG or TPM for 12 weeks. Dual energy X-ray absorptiometry was used to measure bone mineral density. The concentrations of bone metabolism markers were assayed in bone homogenate. In addition, both femurs were measured and used for biomechanical testing. Compared to the control group, both test groups had significantly lower weight, fat mass, whole body and femur BMD, BMC and reduced mechanical strength of bone. All of these changes were more pronounced in rats exposed to LTG. In conclusion, both LTG and TPM significantly reduce BMD and body weight and impair mechanical strength of bone. A question arises as to the degree of dependence of the effect on the dose. Further studies are warranted to establish whether LTG and TPM may have a clinically significant effect on BMD exclusively in the model of gonadectomized rats, or whether the effect applies also in the model of gonadally intact animals, and in the respective human models.

• Klíčová slova
• Antiepileptic drugs, Bone markers, Bone mineral density, Lamotrigine, Topiramate,
• MeSH
• absorpční fotometrie MeSH
• alkalická fosfatasa metabolismus   MeSH
• antikonvulziva aplikace a dávkování   MeSH
• aplikace orální MeSH
• biomechanika účinky léků   MeSH
• ELISA MeSH
• fruktosa analogy a deriváty   farmakologie   MeSH
• kolagen typu I metabolismus   MeSH
• kosti a kostní tkáň účinky léků   metabolismus   MeSH
• kostní denzita účinky léků   MeSH
• kostní morfogenetický protein 2 metabolismus   MeSH
• krysa rodu Rattus MeSH
• lamotrigin MeSH
• modely u zvířat MeSH
• neparametrická statistika MeSH
• orchiektomie MeSH
• osteoprotegerin krev   MeSH
• peptidové fragmenty metabolismus   MeSH
• peptidy metabolismus   MeSH
• potkani Wistar MeSH
• prokolagen metabolismus   MeSH
• složení těla účinky léků   MeSH
• tělesná hmotnost účinky léků   MeSH
• topiramat MeSH
• triaziny aplikace a dávkování   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• alkalická fosfatasa MeSH
• antikonvulziva MeSH
• collagen type I trimeric cross-linked peptide MeSH Prohlížeč
• fruktosa MeSH
• kolagen typu I MeSH
• kostní morfogenetický protein 2 MeSH
• lamotrigin MeSH
• osteoprotegerin MeSH
• peptidové fragmenty MeSH
• peptidy MeSH
• procollagen Type I N-terminal peptide MeSH Prohlížeč
• prokolagen MeSH
• topiramat MeSH
• triaziny MeSH

The prevalence of epilepsy in the world population together with a high percentage of patients resistant to existing antiepileptic drugs (AEDs) stimulates the constant search for new approaches to the treatment of the disease. Previously a significant anticonvulsant potential of cardiac glycoside digoxin has been verified by enhancing a weak activity of AEDs in low doses under screening models of seizures induced by pentylenetetrazole and maximal electroshock. The aim of the present study is to investigate the influence of digoxin at a sub-cardiotonic dose on the anticonvulsant activity of valproate, levetiracetam, and topiramate in models of primary generalized seizures with different neurochemical mechanisms. A total of 264 random-bred male albino mice have been used. AEDs were administered 30 min before seizure induction once intragastrically at conditionally effective (ED50) and sub-effective (½ ED50) doses: sodium valproate and topiramate - at doses of 300 and 150 mg/kg; levetiracetam - at doses of 100 and 50 mg/kg. Digoxin was administered once subcutaneously at a dose of 0.8 mg/kg body weight (1/10 LD50) 10-15 min before seizure induction. Picrotoxin (aqueous solution 2.5 mg/kg, subcutaneously), thiosemicarbazide (aqueous solution 25 mg/kg, intraperitoneally), strychnine (aqueous solution 1.2 mg/kg, subcutaneously), camphor (oil solution 1000 mg/kg, intraperitoneally) have been used as convulsive agents for seizure induction. It was found that under the conditions of primary generalized seizures induced by picrotoxin, thiosemicarbazide, strychnine, and camphor, digoxin not only shows its own strong anticonvulsant activity but also significantly enhances the anticonvulsant potential of classical AEDs sodium valproate, levetiracetam, and topiramate. The obtained results substantiate the expediency of further in-depth study of digoxin as an anticonvulsant drug, in particular, the in-depth study of neurochemical mechanisms of its action.

• Klíčová slova
• adjuvant, anticonvulsant, digoxin, levetiracetam, seizures, topiramate, valproate,
• MeSH
• antikonvulziva * terapeutické užití   MeSH
• digoxin * terapeutické užití   MeSH
• kafr terapeutické užití   MeSH
• kardiotonika terapeutické užití   MeSH
• kyselina valproová * terapeutické užití   MeSH
• levetiracetam * terapeutické užití   MeSH
• myši MeSH
• pikrotoxin MeSH
• strychnin MeSH
• topiramat * terapeutické užití   MeSH
• záchvaty * chemicky indukované   farmakoterapie   prevence a kontrola   MeSH
• zvířata MeSH
• Check Tag
• mužské pohlaví MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• antikonvulziva * MeSH
• digoxin * MeSH
• kafr MeSH
• kardiotonika MeSH
• kyselina valproová * MeSH
• levetiracetam * MeSH
• pikrotoxin MeSH
• strychnin MeSH
• topiramat * MeSH

The present article describes two unrelated cases of progressive myoclonic epilepsy (PME) of the Lafora's disease and Unverricht-Lundborg types who were treated with topiramate (TPM) as add-on therapy for their myoclonus. After the initiation of topiramate therapy both cases responded with marked decrease in myoclonic seizure frequency and improvement of quality of life. Topiramate appears to be a useful alternative agent in cases of PME and could be consider for adjunctive therapy.

• MeSH
• antikonvulziva terapeutické užití   MeSH
• fruktosa analogy a deriváty   terapeutické užití   MeSH
• kombinovaná farmakoterapie MeSH
• lidé MeSH
• mladý dospělý MeSH
• myoklonické epilepsie progresivní farmakoterapie   MeSH
• topiramat MeSH
• Check Tag
• lidé MeSH
• mladý dospělý MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• kazuistiky MeSH
• Názvy látek
• antikonvulziva MeSH
• fruktosa MeSH
• topiramat MeSH

PURPOSE: To study the anticonvulsant action of topiramate (TPM) in developing rats. METHODS: Motor seizures were elicited by administering pentylenetetrazol (100 mg/kg subcutaneously) in five age groups of Wistar rats (7, 12, 18, 25, and 90 days old). TPM was administered intraperitoneally in doses from 10 to 640 mg/kg 2 hours before pentylenetetrazol. The time course of TPM action was studied in 12- and 25-day-old rats up to 24 hours after the 160-mg/kg dose, and the incidence and pattern of seizures were evaluated. RESULTS: TPM did not influence minimal seizures (clonus of forelimb and head muscles with preserved righting ability). Generalized tonic-clonic seizures, however, were reliably changed at all developmental stages studied. The tonic phase was suppressed so that the majority of animals exhibited generalized clonic seizures (with a loss of righting reflexes). In addition, the incidence of generalized seizures was decreased after the 20-, 40-, and 80-mg/kg doses in the 7-day-old rat pups. The specific suppression of the tonic phase of generalized seizures was observed up to 12 hours in the 12-day-old rat pups. The same result was obtained over 6 hours after TPM administration in the 25-day-old animals, and with longer intervals the incidence of generalized seizures decreased in this age group. CONCLUSIONS: TPM exhibits stable anticonvulsant action against the tonic phase of generalized tonic-clonic seizures throughout development. In addition, it suppresses all phases of generalized seizures in 7-day-old rats. The anticonvulsant action of TPM lasted longer in 25-day-old than in 12-day-old rats. The two actions of TPM might be ascribed to two different mechanisms of action.

• MeSH
• antikonvulziva aplikace a dávkování   farmakologie   MeSH
• chování zvířat účinky léků   MeSH
• epilepsie generalizovaná chemicky indukované   prevence a kontrola   MeSH
• epilepsie tonicko-klonická chemicky indukované   prevence a kontrola   MeSH
• fruktosa aplikace a dávkování   analogy a deriváty   farmakologie   MeSH
• injekce intraperitoneální MeSH
• krysa rodu Rattus MeSH
• modely nemocí na zvířatech MeSH
• mozek účinky léků   růst a vývoj   MeSH
• pentylentetrazol MeSH
• pohybová aktivita účinky léků   MeSH
• potkani Wistar MeSH
• topiramat MeSH
• věkové faktory MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• antikonvulziva MeSH
• fruktosa MeSH
• pentylentetrazol MeSH
• topiramat MeSH

Administration of many antiepileptic drugs to patients with porphyria can precipitate an acute porphyric crisis. Information on the porphyrogenic activity of new antiepileptic drugs is still limited. In the presented study, the effects of tiagabine and topiramate on porphyrin metabolism were evaluated in an in vivo model of porphyria. Administration of the protoporphyrinogen oxidase inhibitor oxadiazon (12.5 mg/kg/day) for four days to male Wistar rats caused a partial block of porphyrin biosynthesis, thus mimicking the condition of quiescent variegate porphyria. Administration of phenobarbital (75 mg/kg/day) to oxadiazon-pretreated rats increased liver porphyrin content, liver porphobilinogen content (means 480 nmol/g, control less than 20 nmol/g) and urinary excretion of porphobilinogen (means 1,000 micromol/l, control less than 20 micromol/l). Tiagabine (75 mg/kg/day) and topiramate (75 mg/kg/day) increased liver porphobilinogen content (means 33 and 53 nmol/g respectively) and urinary porphobilinogen concentration (240 and 490 micromol/l respectively). Similar results were obtained in oxadiazon-treated BALB/c mice. In untreated rats, tiagabine and topiramate caused a moderate increase of hepatic pentoxyresorufin-O-dealkylase activity (approximately 100 and 200 pmol/min./mg respectively, controls 15 pmol/min./mg). These data demonstrate that administration of tiagabine or topiramate to oxadiazon-treated animals can provoke a condition resembling an acute porphyric attack and suggest that administration of these drugs to patients with suspected porphyria should be avoided. However, 5-day administration of both tiagabine and topiramate (75 mg/kg) is considerably less porphyrogenic than phenobarbital administered at the same dose.

• MeSH
• antikonvulziva farmakologie   MeSH
• fenobarbital farmakologie   MeSH
• fruktosa analogy a deriváty   farmakologie   MeSH
• herbicidy farmakologie   MeSH
• játra účinky léků   metabolismus   MeSH
• krysa rodu Rattus MeSH
• kyseliny nipekotinové farmakologie   MeSH
• ledviny účinky léků   metabolismus   MeSH
• lékové interakce MeSH
• myši inbrední BALB C MeSH
• myši MeSH
• oxadiazoly farmakologie   MeSH
• oxidoreduktasy působící na CH-CH vazby * MeSH
• oxidoreduktasy antagonisté a inhibitory   MeSH
• porfyrie chemicky indukované   MeSH
• porfyriny biosyntéza   metabolismus   MeSH
• potkani Wistar MeSH
• protoporfyrinogenoxidasa MeSH
• tiagabin MeSH
• topiramat MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• mužské pohlaví MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• antikonvulziva MeSH
• fenobarbital MeSH
• fruktosa MeSH
• herbicidy MeSH
• kyseliny nipekotinové MeSH
• oxadiazoly MeSH
• oxadiazon MeSH Prohlížeč
• oxidoreduktasy působící na CH-CH vazby * MeSH
• oxidoreduktasy MeSH
• porfyriny MeSH
• protoporfyrinogenoxidasa MeSH
• tiagabin MeSH
• topiramat MeSH