-
The American Journal of Psychiatry Aug 1997
Topics: Adult; Ammonia; Bipolar Disorder; Carbamoyl-Phosphate Synthase (Ammonia); Carnitine; Depressive Disorder; Drug Administration Schedule; Female; Humans; Urea; Valproic Acid
PubMed: 9247410
DOI: 10.1176/ajp.154.8.1168 -
Epilepsia Apr 1982The pharmacokinetics of valproic acid were investigated in six healthy volunteers. After a single intravenous dose of 1,000 mg valproic acid, the pharmacokinetic...
The pharmacokinetics of valproic acid were investigated in six healthy volunteers. After a single intravenous dose of 1,000 mg valproic acid, the pharmacokinetic parameters were determined according to the open two-compartment model. Bioavailability of valproic acid was performed comparing the areas under curves (AUC) after i.v and an equal single oral dose. The half-life of the initial phase was t 1/2 alpha = 0.64 +/- 0.32 h, and the elimination half-life was calculated as t 1/2 beta = 11.55 +/- 2.33 h. The distribution volume of the central compartment was Vc = 9.9 +/- 0.78 L, the apparent volume of distribution was Vd beta = 18.2 +/- 6.2 L, and the distribution volume at steady state was Vss = 12.6 +/- 1.2 L. The value for the average total clearance was Cltot = 51.1 +/- 11.9 ml/min. The study showed that in comparison to single dosing, the elimination half-life increased in average for four hours after multiple dosing (p less than or equal to 0.05). There was only a poor correlation between serum concentrations and concentration of valproic acid in saliva (r = 0.42).
Topics: Administration, Oral; Capsules; Humans; Infusions, Parenteral; Kinetics; Saliva; Valproic Acid
PubMed: 6804223
DOI: 10.1111/j.1528-1157.1982.tb05063.x -
Pharmacokinetics of valproic acid after administration of three oral formulations in healthy adults.The Journal of the Association of... Sep 1990The pharmacokinetics and bioavailability of valproic acid was compared in six healthy volunteers after single dose oral administration of 400 mg of the drug in tablet,... (Comparative Study)
Comparative Study
The pharmacokinetics and bioavailability of valproic acid was compared in six healthy volunteers after single dose oral administration of 400 mg of the drug in tablet, capsule and syrup form in a crossover manner. Blood samples were collected for 48 hours and valproic acid concentration analysed by enzymatic immunoassay. Following the administration of the three dosage forms, the absorption varied (Ka = Syrup K 2.64 +/- 0.5; tablet 1.57 +/- 0.22; and capsule 0.55 +/- 0.55 h-1). Valproic acid concentration reached a peak level of 102.3 micrograms.ml at 1.9 h after syrup administration, 73 micrograms/ml at 3.3 h after tablet and 44.8 micrograms/ml at 5.4 h after capsule. The bioavailability of tablet and syrup formulation was not significantly different from each other but it differed from capsule form in that the bioavailability was only 52%.
Topics: Administration, Oral; Adolescent; Biological Availability; Capsules; Humans; Tablets; Therapeutic Equivalency; Valproic Acid
PubMed: 2266076
DOI: No ID Found -
Zhurnal Nevrologii I Psikhiatrii Imeni... 2017The article summarizes domestic and international studies on the development and clinical investigation of valproates including multiple studies of a research team... (Review)
Review
The article summarizes domestic and international studies on the development and clinical investigation of valproates including multiple studies of a research team directed by the author. Valproate targets are considered in biological and clinical aspects. A spectrum of action and advantages of the brand drug (depakine) compared to generics and other antiepileptic drugs are discussed. A number of recommendations for practitioners about using valproates are proposed.
Topics: Anticonvulsants; Drugs, Generic; Epilepsy; GABA Agents; Humans; Russia; Valproic Acid
PubMed: 29265098
DOI: 10.17116/jnevro2017117111129-134 -
Pediatric Neurology Sep 2004Concomitant administration of meropenem has been reported to decrease serum level of valproic acid both in humans and in animals. This report describes three children...
Concomitant administration of meropenem has been reported to decrease serum level of valproic acid both in humans and in animals. This report describes three children who required simultaneous administration of valproic acid and meropenem. Meropenem rapidly decreased serum valproic acid concentration to subtherapeutic levels in all three children, and serum valproic acid levels were returned to therapeutic levels in a short time after discontinuing simultaneous meropenem therapy. Valproic acid was not changed to another antiepileptic agent, because no seizure activity was observed. To our knowledge, this is the first case report on the simultaneous administration of meropenem and valproic acid in childhood. In conclusion, it is clear that concomitant meropenem administration decreases serum valproic acid concentration, and we believe that there may be no need to change the antiepileptic drug during this period, provided that the patient has no seizure. More detailed studies are required.
Topics: Adolescent; Drug Interactions; Drug Therapy, Combination; Female; Humans; Infant; Male; Meropenem; Thienamycins; Valproic Acid
PubMed: 15351028
DOI: 10.1016/j.pediatrneurol.2004.03.014 -
Fundamental and Applied Toxicology :... May 1986The antiepileptic drug valproic acid (VPA) was administered via four different routes in the mouse during gestational stages sensitive for interference with neural tube...
Valproic acid teratogenicity in mice after various administration and phenobarbital-pretreatment regimens: the parent drug and not one of the metabolites assayed is implicated as teratogen.
The antiepileptic drug valproic acid (VPA) was administered via four different routes in the mouse during gestational stages sensitive for interference with neural tube defect formation: a single oral intubation or injection, sc or ip, on Day 8, or infusion via subcutaneously implanted osmotic minipumps from Day 7 1/2 to 8 1/2 of gestation. Embryotoxicity was evaluated on Day 18 (incidence of exencephaly, embryolethality and fetal weight retardation). Oral intubation of VPA resulted in significantly lower peak concentrations of VPA as well as lower embryotoxicity as compared to sc and ip administration. The metabolites of the beta-, omega- and omega-1 oxidation pathways were present in both maternal serum and gestational tissues in very low concentrations (usually less than 2% of corresponding VPA levels). Infusion of VPA via osmotic minipumps (lower steady-state VPA levels as compared to peak levels following injection of VPA) resulted in embryolethality and fetal weight retardation, but little exencephaly. The metabolic pattern was similar in all four administration experiments. Phenobarbital pretreatment of the dams (previously shown to reduce VPA serum concentrations and induce the omega- and omega-1 oxidation pathways) reduced the embryotoxicity of VPA. These results suggest that VPA embryotoxicity is mediated by the parent drug, and not one of the metabolites considered in this study.
Topics: Administration, Oral; Animals; Biotransformation; Female; Injections, Intraperitoneal; Injections, Subcutaneous; Mice; Neural Tube Defects; Phenobarbital; Pregnancy; Teratogens; Valproic Acid
PubMed: 3086173
DOI: 10.1016/0272-0590(86)90179-x -
The New Zealand Medical Journal Oct 1979
Topics: Adult; Animals; Brain; Child; Epilepsy; Epilepsy, Absence; Female; Hemostasis; Humans; Pregnancy; Valproic Acid
PubMed: 117405
DOI: No ID Found -
Journal of Pharmacokinetics and... Aug 2013Plasma concentration-time data obtained after an oral single dose of 500-mg valproic acid (VPA) in a delayed release formulation was used to model enterohepatic cycling... (Randomized Controlled Trial)
Randomized Controlled Trial
Plasma concentration-time data obtained after an oral single dose of 500-mg valproic acid (VPA) in a delayed release formulation was used to model enterohepatic cycling of the drug. Fourteen healthy subjects (seven women and seven men) were enrolled, food intake was standardized, blood samples were withdrawn up to 48 h post dosing and VPA plasma concentrations were analyzed by HPLC-UV method. Secondary peaks of VPA were observed in almost all subjects. A population pharmacokinetic analysis with sex, weight, age and contraceptive therapy as possible covariates was performed. Women without contraceptive therapy presented a longer lag time, a lower VPA hepatic output and a higher reabsorbed fraction than men. Weight affected both volume of the central compartment and the absorption rate constant. Women under contraceptive therapy showed similar disposition parameters to men. Reabsorbed fraction of bioavailable dose was 46.2 % in women and 21.8 % in men, revealing important sex differences in drug hepatobiliar output. These results showed that VPA displays sex-related pharmacokinetic differences due to different metabolic and transporter-mediated disposition.
Topics: Absorption; Administration, Oral; Adult; Cross-Over Studies; Female; Humans; Male; Sex Factors; Valproic Acid; Young Adult
PubMed: 23784346
DOI: 10.1007/s10928-013-9323-3 -
The Canadian Journal of Neurological... Nov 1978Valproic acid is a new antiepileptic drug recently introduced in the United States for the treatment of absence seizures. In this study on patients with absence and...
Valproic acid is a new antiepileptic drug recently introduced in the United States for the treatment of absence seizures. In this study on patients with absence and other seizure types, the majority of patients achieved optimal control within four weeks of therapy. No patient responded to valproic acid who did not show an initial clinical response by four weeks of active therapy. Optimal response was generally achieved when plasma levels were greater than 55 microgram/ml. Excellent clinical response was observed in the treatment of absence and myoclonic seizures. Twenty-two patients continued in a long term study have maintained the same degree of seizure control as observed at the time of optimal control.
Topics: Adolescent; Adult; Epilepsies, Myoclonic; Epilepsy; Epilepsy, Absence; Female; Humans; Male; Valproic Acid
PubMed: 105796
DOI: 10.1017/s0317167100024148 -
Drug Metabolism and Disposition: the... Jan 2003In this study, spectroscopic and chromatographic evidence is presented for the identification and characterization of the metabolites, valproyl glutamate... (Comparative Study)
Comparative Study
In this study, spectroscopic and chromatographic evidence is presented for the identification and characterization of the metabolites, valproyl glutamate (2-propylpentanoyl glutamate, VPA-GLU) and valproyl glutamine (2-propylpentanoyl glutamine, VPA-GLN) in the urine, serum, and cerebrospinal fluid (CSF) of patients on valproic acid (VPA) therapy. Moreover, the identification of valproyl glycine (2-propylpentanoyl glycine, VPA-GLY) in the serum and urine of patients on VPA, albeit in trace concentrations, is also reported here. The three amino acid conjugates excreted in urine accounted for about 1% of the VPA dose in four patients who were on VPA therapy chronically and had reached steady state. VPA-GLU was quantitatively the most prominent metabolite (0.66-13.1 microg/mg creatinine) compared with VPA-GLN (0.78-9.93 microg/mg creatinine) and VPA-GLY (trace-1.0 microg/mg creatinine) in overnight urine samples of all patients studied (n = 29). The relatively low serum concentrations of the three amino acid conjugates of VPA in six patients suggest that the metabolites are readily excreted once formed. In contrast, whereas VPA GLY was absent in the CSF of one patient on VPA, the concentrations of VPA-GLU and VPA-GLN in this CSF sample were 9 and 5 times, respectively, their corresponding serum concentrations.
Topics: Adolescent; Amino Acids; Child; Epilepsy; Esters; Gas Chromatography-Mass Spectrometry; Humans; Valproic Acid
PubMed: 12485960
DOI: 10.1124/dmd.31.1.114