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Biomedical subjects

H J Villarreal

Publications and source records attributed to H J Villarreal.

11 recordsLinked to original sources
PubMed1982

In vivo uptake of valproic acid into brain.

The pharmacokinetics of valproic acid (VPA) penetration into the central nervous system of cats were studied. VPA levels in cortical gray matter and plasma were measured at timed intervals after rapid intravenous drug infusion. Brain uptake of the drug was maximal at 1 min postinfusion and decayed rapidly with a mean elimination half-life of 41 min. After a rapid distribution phase, plasma VPA levels remained stable for 90 min. The brain:plasma ratio was maximal at 1 min and also declined rapidly. The volume of distribution was 0.125 1/kg. The small volume of distribution, low brain:plasma ratios and rapid clearance from brain indicate that VPA is not significantly bound in cerebral cortex after a single dose.

Animals↗
PubMed1980

Effects of intracortical injection of blood and blood components on the electrocorticogram.

Long term effects of the intracortical implantation of blood and blood products on the electrocorticogram were studied in cats and guinea pigs. Focal epileptiform paroxysmal discharges developed after implantation of whole blood, hemolyzed erythrocytes, methemoglobin, ferritin, ferrous chloride, ferric chloride, fibrinogen, hemin, and cottonoid. In each group recurrent paroxysmal discharges became more prominent and more frequent after several months, suggesting a physiological change caused by a breakdown product of blood. The lesions were characterized by varying degrees of cell loss, iron deposition and glial proliferation. It is thought that posttraumatic epilepsy, which is frequently accompanied by extravasation of blood into the brain, might share a similar physiopathogenesis.

Animals↗
PubMed1980

Valproic acid and plasma levels of phenobarbital.

During concurrent administration of phenobarbital and valproic acid, phenobarbital plasma concentrations often increase. This often requires a reduction of phenobarbital dosage. In normal cats and patients with epilepsy, we found no evidence of decreased renal excretion of phenobarbital. Metabolic studies in four patients revealed a decrease in the conversion of phenobarbital to hydroxyphenylphenobarbital and decreased urinary ratios of hydroxyphenylphenobarbital to phenobarbital. These data suggest that phenobarbital metabolism is inhibited by therapeutic plasma levels of valproic acid.

Adult↗
PubMed1978

Steady-state kinetics of valproic acid in epileptic patients.

Pharmacokinetic evaluation and prediction were carried out in 20 epileptic patients. Using conventional pharmacokinetic techniques and a one-compartment model, predicted and observed valproic acid plasma concentrations were compared. Valproic acid assay was performed by gas-liquid chromatography. There was good agreement between predicted and observed plasma concentrations. Most patients had predicted half-lives (t1/2s) of 6 to 8 hr, independent of the plasma concentration of valproic acid. Five patients had predicted t1/2s of 12 hr. The correlation between dose and plasma level was poor. Most patients had valproic acid plasma levels between 55 and 100 microgram/ml. Administration of valproic acid three times a day with determination of individual plasma concentrations offers a reliable method of monitoring. Constant levels are maintained in individual patients, but there is substantial intersubject variation.

Adolescent↗
PubMed1978

Clinical efficacy of valproic acid in relation to plasma levels.

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.

Adolescent↗
PubMed1978

Effect of valproic acid on spike and wave discharges in patients with absence seizures.

Twenty-five patients with absence seizures were treated with valproic acid in doses from 17 to 62.5 mg per kilogram per day. Nineteen patients experienced reduction of spike and wave discharges; in 11 it was greater than 75 percent. Twenty-one patients had a reduction of the total time of spike and wave discharge. Four patients had increase of spike and wave discharges. Nineteen patients had fewer absence seizures. There was no correlation between plasma concentration of valproic acid and EEG change, but clinical improvement occurred when plasma levels of valproic acid reached 50 to 60 microgram per milliliter.

Adolescent↗
PubMed1978

Valproic acid: interaction with other anticonvulsant drugs.

The interaction of valproic acid and other antiepileptic drugs was studied in 25 patients for 5 to 9 months. Clinical evaluations, seizure records, and antiepileptic drug levels were followed regularly. Eleven of the 13 patients required a reduced phenobarbital dose when concurrently treated with valproic acid. This reduction was prompted by sedation. An average dose reduction of 46 percent resulted in an average serum phenobarbital decrease of 15 percent. Ten of 15 patients had decreased phenytoin concentrations during concurrent administration with valproic acid. No definitive conclusion was reached about other antiepileptic drugs. Decreased phenobarbital excretion because of urine acidification and displacement of phenytoin from protein binding sites may account for the observations. Careful monitoring of anticonvulsant levels is required in anticipation of the documented interactions.

Adolescent↗
PubMed1978

Effect of valproic acid on hepatic function.

Altered hepatic function tests occurred in four of 25 patients treated with valproic acid. An average dose reduction in three patients of 10 mg per kilogram per day resulted in reversion of serum glutamic oxaloacetic transaminase (SGOT) and serum glutamic pyruvic transaminase (SGPT) to normal. The drug was discontinued in one patient. Careful monitoring of hepatic function is required of patients being treated with valproic acid, but our experience suggests that dose reduction alone may be effective in preventing untoward hepatic side effects.

Adolescent↗
PubMedDate not supplied

[Thallium poisoning. Experience with 50 patients].

We have studied fifty cases of thallium intoxication during the past nine years. Twenty-eight occurred in women and twenty-two in men. One of the patients was a new born whose mother had this type of intoxication during her third trimester of pregnancy. The ages varied from one day to 84 years and in all cases the source of thallium was ingestion of rat poison, except for the baby who received it across the placenta and an other patient whose source was transdermal. Twenty-three of the cases of intoxication were accidental, twenty-one were suicidal attempts and five were homicidal. One case did not know the source of intoxication. Thallium levels were measured in the urine of all the patients, some were measured in blood, as well as cerebrospinal fluid. The main clinical manifestation was a mixed type of severe peripheral neuropathy, with abdominal pain, nausea, vomiting and alopecia and some cases had psychiatric manifestations. Electrophysiological studies and nerve biopsy examined with electron microscopy in three patients. Magnetic nuclear resonance, computerized axial tomography of the abdomen and cranium were performed in two patients. There was only one death and the rest of the patients recovered almost completely. Pathophysiology and pharmacological management of this type of neurointoxication are revised.

Abnormalities, Multiple↗