The toxicity and pharmacokinetic properties of a drug determine whether hemodialysis and/or hemoperfusion are indicated in acute intoxications. Valproic acid is considered unremovable by hemodialysis because of the high protein binding of 90%-95%. A 27-year-old male with a history of seizures was admitted to the emergency room because of coma, ...

Toxicity occurs rapidly after overdose with regular-release valproic acid, but there is less experience with enteric-coated formulations. We report a case of delayed onset of toxicity and time to peak levels after ingestion of enteric-coated divalproex sodium (Epival). The patient was a 24-year-old female who ingested an unknown amount of ...

BACKGROUND AND OBJECTIVES: Fibrinolytic activity of urine may rapidly degrade fibrin glue used in the urinary tract, thereby limiting tissue adhesion. The goals of this study were to verify the ability of antifibrinolytic agents to delay the degradation of fibrin glue in the urinary tract and to assess the results ...

BACKGROUND: Epsilon-aminocaproic acid is routinely used to reduce bleeding during cardiac surgery. Anecdotal reports of thrombotic complications have led to speculation regarding this drug's safety. We investigated the association between epsilon-aminocaproic acid administration and postoperative stroke. METHODS: Six thousand two hundred ninety-eight patients undergoing isolated coronary artery bypass graft surgery ...

BACKGROUND: Divalproex sodium has been reported to be better tolerated than valproic acid. To our knowledge, no study has examined whether significant differences in the tolerability and efficacy exist between these preparations in psychiatric patients. The objective of the present study was to compare the tolerability and efficacy of divalproex ...

This study was designed to distinguish and evaluate the contribution of reactive metabolite and reactive oxygen species as the mechanism of metabolism-dependent valproic acid-induced in vitro cytotoxicity. The involvement of reactive oxygen species in the mechanism of in vitro cytotoxicity was examined by the addition of a series of antioxidant ...

Epsilon-aminocaproic acid (Amicar) is used to treat severe hemorrhage refractory to usual medical management. This antifibrinolytic drug has been associated with a number of renal complications. However, there are no descriptions of this medication causing hyperkalemia. This report describes the development of hyperkalemia in a patient with underlying chronic renal ...

We studied the efficacy of felbamate (FBM) in combination with valproic acid (VPA) in 13 patients with the Lennox-Gastaut syndrome and evaluated the contribution of each drug. Following stabilization on VPA monotherapy, FBM or placebo titration was performed for two observation periods lasting 7 weeks with a washout period between ...

To elucidate the etiology of valproic acid-induced carnitine deficiency, we tested the hypothesis that long-term valproic acid administration decreases the rate of carnitine reabsorption. Thirteen healthy men participated in a 34-day protocol in which carnitine clearance was measured before and after 28 days of valproic acid administration. During valproic acid ...

The effects of four valproic acid derivatives were studied on pentylenetetrazole-induced epileptiform discharges in combined entorhinal cortex hippocampus slices. The two new sugar-esters of valproic acid, dimethylenexylitol valproate (VDMX, 0.5 mM) and glucose valproate (VG, 2 mM) abolished the epileptiform activity. These two new derivatives were compared to two clinically ...

OBJECTIVE: To report a patient who developed the paradoxical effect of increasing electrical seizure activity and confusion with initiation of valproic acid therapy. CASE SUMMARY: A 25-year-old African-American woman with a hypothalamic hamartoma had an electroencephalogram (EEG) that demonstrated frequent bursts of generalized spike and wave activity. The prevalence of ...

In a prospective open-label study, the substitution of immediate-release valproic acid for divalproex sodium was evaluated in the treatment of 47 adult psychiatric inpatients who had been stabilized on divalproex for at least one month. After two weeks, no significant change in Clinical Global Impressions scale (CGI) scores or in ...

BACKGROUND: Tranexamic acid has been shown to greatly reduce the incidence of secondary hemorrhage when administered orally or intravenously. Topical administration of the drug should result in much lower serum concentrations, with fewer adverse effects. We performed a study to determine whether topical application of tranexamic acid would yield higher ...

Maximum blood concentrations (Cmax) of thrombin and tranexamic acid were evaluated in the bloodstream after local application of a radioactively labelled cryoprecipitate based fibrin (CBF) sealant to a partial liver resection in rabbits. The Cmax of 3H-tranexamic acid reached a peak of 0.015 mg/ml of plasma after 1 h and ...

Valproic acid, a well known anticonvulsant, is being used by psychiatrists increasingly to manage bipolar and other affective disorders. Because of the demographics of the population affected by such psychiatric conditions, more women of childbearing age are likely to be exposed to this teratogenic drug. Neural tube defects (NTD) are ...

(1) Pamidronic acid has no demonstrated influence on the survival time in patients with myeloma or bone metastases. (2) Two comparative placebo-controlled trials involving women with metastatic breast cancer show that a monthly infusion of pamidronic acid reduces the number of patients needing analgesic bone irradiation. It is not known ...

Zidovudine (3'-azido-3'-deoxythymidine [AZT]), an antiviral nucleoside analog effective in the treatment of human immunodeficiency virus infection, is primarily metabolized to an inactive glucuronide form, GAZT, via uridine-5'-diphospho-glucuronosyltransferase (UGT) enzymes. UGT enzymes exist as different isoforms, each exhibiting substrate specificity. Published clinical studies have shown that atovaquone, fluconazole, methadone, and valproic ...

The toxicities of benzoic acids to Vibrio fischeri, Daphnia magna and carp were measured. The results showed that the toxicity to V. fischeri and Daphnia decreased in the order of bromo > chloro > fluoro approximately equal to aminobenzoic acids. The toxicity of substituted benzoic acids to carp and Daphnia ...

This study investigates the influence of L-carnitine supplementation on valproic acid concentrations in rat serum, brain, and liver. Carnitine supplementation increased carnitine concentrations significantly in serum and liver but not in the brain. Free valproic acid concentrations in the brain were significantly increased by carnitine supplementation without any change of ...

Antifibrinolytic agents, epsilon-aminocaproic acid (EACA) and tranexamic acid (TXA), have been reported to be efficacious in the treatment of chronic persistent epithelial defects. Within the regulatory mechanism of corneal reepithelialization, fibronectin serves as a primary adhesive component in the healing process and anchors regenerating epithelial cells to underlying stroma. EACA ...

The in vivo teratogenic potential of valproic acid (VPA) and related teratogenic and non-teratogenic analogues has been correlated with their effects on specific in vitro endpoints of cell proliferation, migration and CAM-dependent neurite outgrowth, as these events are common to crucial epochs of development. The (+/-)-2-n-propyl-4-pentynoic acid [(+/-)-4-yn-VPA] and S-2-n-propyl-4-pentynoic ...

1. This study compared the effects of the antimanic drugs, lithium and valproic acid, on GABA and glutamine CSF concentration and on head-shakes during hyponatremia. 2. Hyponatremic and normonatremic rats were treated with 2 mEq/kg lithium and 360 mg/kg valproic acid. Behavioral observation was conducted for 120 min after which ...

OBJECTIVE: Nonlinear mixed-effects modeling (NONMEM) was used to estimate the effects of drug drug interaction on phenobarbitone clearance values, using 648 serum levels gathered during the routine clinical care of 349 pediatric and adult epileptic patients (age range, 0.4-33.3 years). Patients received phenobarbitone as monotherapy or in combination with either ...

One of the possible unwanted side effects following contact immunotherapy of alopecia areata is skin hypopigmentation, either in the form of a transient, post-inflammatory hypopigmentation or as the development of a persistent, depigmented patch. A case of leucoderma occurring on the forehead of a 16-year-old girl following application of squaric ...

The teratogenic properties of valproic acid (VPA) and its analogues depend to a great extent on their chemical structure. We investigated the structure-teratogenicity relationships of VPA, its structural isomer, valnoctic acid (VCA), and their two amide analogues, valpromide (VPD) and valnoctamide (VCD), respectively. Each substance was injected (3 mmol/kg) in ...

BACKGROUND: The efficacy of prophylactic epsilon-aminocaproic acid and tranexamic acid to reduce transfusions after primary myocardial revascularization was evaluated in a teaching hospital context. METHODS: Patients (n = 134) received either epsilon-aminocaproic acid (15-g bolus + infusion of 1 g/h), high-dose tranexamic acid (10-g bolus + placebo infusion), or normal ...

The effects of fatty acids, including oleate, on the interaction between furosemide and valproic acid in sera at respective serum therapeutic concentration levels were investigated using an ultrafiltration technique. The free fraction of furosemide was significantly increased in the presence of valproic acid. Mutual displacement experiments indicated that furosemide and ...

Nonlinear mixed effects modeling (NONMEM) was used to estimate the effects of drug-drug interaction on valproic acid relative clearance values using 792 serum levels gathered from 400 pediatric and adult patients with epilepsy (age range, 0.3-54.8 years) during their clinical routine care. Patients received valproic acid as monopharmacy or in ...

Concern about the side effects of allogeneic red blood cell transfusion has increased interest in methods of minimizing perioperative transfusion. We performed meta-analyses of randomized trials evaluating the efficacy and safety of aprotinin, desmopressin, tranexamic acid, and epsilon-aminocaproic acid in cardiac surgery. All identified randomized trials in cardiac surgery were ...

In an 8-week open-trial substitution study, 64 subjects with seizure disorders living at an ICF/MR were randomly assigned to either brand-named Depakene or generic Valproic Acid USP (Solvay) medication. After 4 weeks, they were switched to the other medication. Blood levels and seizures were monitored. The price of the generic ...

Cytochrome P450-dependent desaturation of the anticonvulsant drug valproic acid (VPA) results in formation of the hepatotoxin, 4-ene-VPA. Polytherapy with other anticonvulsants which are known P450 inducers increases the flux through this bioactivation pathway. The aim of the present study was to identify specific, inducible forms of human liver P450 which ...

Valproic acid (VPA), a synthetic branched-chain fatty acid, and its pro-drug the primary amide (VPD) are effective and widely used anti-epileptic agents. Although the use of VPA has grown in recent years, major side effects are still associated with this drug. We presume that it is possible, without loosing the ...

Valproyl glycinamide (TV 1901-VPGD) is a new antiepileptic drug, which is currently undergoing clinical trials. The present study explored the pharmacokinetics and pharmacodynamics (anticonvulsant activity and neurotoxicity) of two new isomers of valproyl glycinamide: valnoctyl glycinamide (VCGD) and diisopropylacetyl (DIGD). Both VCGD and DIGD showed anticonvulsant activity and a safety ...

Valproic acid is an effective antiseizure medication that is also used for other indications such as migraine prophylaxis. It is known to sometimes cause hepatic injury, both a mild dose-related form and an idiosyncratic, fulminant, usually fatal type. A case is reported of multiorgan failure caused by valproic acid toxicity ...

OBJECTIVES: To determine whether topically applied aminocaproic acid, like systemic aminocaproic acid, effectively reduces secondary hemorrhage after hyphemas and to compare the safety and effectiveness of topical application with those of systemic use and a control group. DESIGN: A prospective, randomized, double-masked, multicenter study. PATIENTS: Sixty-four patients with traumatic hyphema ...

The impact of replacing divalproex sodium with valproic acid on patient outcomes and direct drug costs was studied. Before-and-after medical chart review was performed in a state-supported facility for mentally retarded adults in which a pharmacy and therapeutics (P&T) committee recommended replacement of divalproex with valproic acid. Patients were studied ...

PURPOSE: We evaluated the efficacy of direct hemoperfusion (DHP) for treatment of acute valproate (VPA) intoxication and speculate on the biochemical perturbations that suggest a mechanism of coma induced by VPA overdose. PATIENT AND METHODS: The comatose patient was hospitalized approximately 6 h after ingesting 18 g VPA. DHP, with ...

Because wounding the epidermis increases proteolytic activity and because disorders associated with barrier dysfunction have elevated protease activity, we studied the effect of protease inhibitors on the time course of barrier recovery and on the development of epidermal hyperplasia induced by repeated injury. After injuries to the epidermis produced by ...

Ketoconazole is an antifungal agent widely used in the management of patients with fungal infection, especially in patients with acute acquired immuno-deficiency syndrome (AIDS). Ketoconazole is 99% bound to serum albumin and may interact with valproic acid, an anticonvulsant with 90% to 95% binding to serum albumin. The interaction may ...

Cell expression of inducible nitric oxide synthase (iNOS) is increased by cytokines, which results in high endogenous concentrations of nitric oxide (NO) and has been implicated in organ injury, including myocardial reperfusion injury. Serine protease inhibitors reduce cytokine-induced iNOS expression. The protease inhibitors aprotinin and tranexamic acid, which are used ...

We previously reported the in vitro differential stereoselective dysmorphogenic potential of the R(+) and S(-) enantiomers of 2n-propyl-4-pentynoic acid (4-yn-VPA) in mice. To determine whether this stereoselectivity is species specific, we evaluated the dysmorphogenic potential of these isomers as well as valproic acid (VPA) to gestational day 9 rat embryos ...

The present study shows that the multifactorial genetic liability to spontaneous exencephaly in the SELH/Bc mouse strain (10-20% of embryos) also confers an elevated risk of exencephaly induced by valproic acid. Treatment of pregnant dams (600 mg/kg sodium valproate in distilled water, i.p.) during the critical period on day 8 ...

Valproic acid is an anticonvulsant drug known to inhibit the glucuronidation of zidovudine (AZT) in human liver microsomes. Zidovudine is metabolized by glucuronidation to the inactive 5'-glucuronide with a short plasma half-life (1.0 +/- 0.2 hour). This case presentation confirms that valproic acid inhibits glucuronidation in vivo, and this is ...

BACKGROUND: Although topically applied all-trans-retinoic acid (tretinoin) undergoes minimal absorption and adds negligibly to normal endogenous levels, its safety in humans is occasionally questioned because oral ingestion of retinoids at therapeutic levels is known to entail teratogenic risks. OBJECTIVE: To assess the actual potential for developmental toxicity from treatment with ...

PURPOSE: To explore the utilization of seven novel hydroxamic acid derivatives of valproic acid (VPA) as new antiepileptics. METHODS: The study was carried out by investigating the pharmacokinetics of two active compounds in dogs and pharmacodynamics (anticonvulsant activity and neurotoxicity) of valproyl hydroxamic acid and six of its derivatives. RESULTS: ...

Higher concentrations of free valproic acid and phenytoin have been reported in patients with uremia and liver disease. Free fatty acids also displace valproic acid and phenytoin. This is a study of the magnitude of displacement of valproic acid and phenytoin from protein binding by free fatty acid in lipemic ...

The contribution of the anticonvulsant agent, valproic acid, to the interaction between neuromuscular blockers and anticonvulsants remains unclear. Therefore, this study was undertaken to examine the acute neuromuscular effects of valproic acid and its potential for interaction with neuromuscular blocking drugs. Phrenic nerve-hemidiaphragm preparations from rats were mounted in modified ...

A short history of the research work of S. Okamoto and co-workers, for the previous 50 years, is briefly described. In the 1950s, when the physiologic role of fibrinolysis had not been established, they began to seek for compounds that inhibit the action of plasmin. They examined approximately 200 lysine ...

Valproic acid, a primary anticonvulsant drug, has recently been studied for purported effectiveness in disparate disorders of mood and behaviour. The psychopharmacological treatment of patients with acquired brain injury frequently includes numerous trials of psychotherapeutic drugs such as antipsychotics, benzodiazepines, antidepressants, and lithium, in an effort towards affective and behavioural ...

OBJECTIVE: To describe a patient in whom the administration of tiaprofenic acid and fosinopril was associated with decreased lithium clearance, resulting in increased serum lithium concentrations. CASE SUMMARY: A woman treated with lithium for bipolar affective disorder was concurrently treated with tiaprofenic acid 200 mg tid for shoulder pain. Previously ...