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At least 793 records · Page 44Linked to original sources
PubMed1978

Serum protein binding and pharmacokinetics of valproate in man, dog, rat and mouse.

The serum protein binding of valproate (di-n-propylacetate) has been determined at therapeutic concentrations by equilibrium dialysis in man (94.8%), dog (78.5%), rat (63.4%) and mouse (11.9%). In dog serum, the binding was found to be independent of the valproate concentration in the range of 5 to about 70 microgram/ml, but fell with higher concentrations. In addition, the kinetics of valproate has been determined in dogs and rats. After intravenous administration, serum concentrations declined biexponentially in both species, the half-life of elimination (T 0.5 (beta)) being 1.7 hours in dogs and 4.6 hours in rats. In comparison with the pharmacokinetics of valproate in man and mouse, it can be assumed that the protein binding of valproate is rate-limiting for its clearance by the liver and may be responsible for the striking differences in the half-lives of the drug in different species. Increased drug binding was associated with a decrease in the total clearance and in all species examined, the calculated hepatic extraction ratios (0.009-0,17) were smaller that the free fraction, indicating that valproate fits into the group of drugs with restrictive and liver blood flow independent elimination, i.e., only the unbound drug can be cleared.

Animals↗
PubMed1978

Sodium valproate (Epilim) in the treatment of refractory epilepsy.

Sodium valproate was given to seven children with refractory epilepsy and mental retardation. Four of the children became fit free while another was much improved. Plasma levels of sodium valproate correlated well with the dose prescribed and did not approach the theoretical top-desirable level of 200 microgram/ml despite larger than recommended doses. Side effects were minimal and it is concluded that the drug is safe and useful.

Adolescent↗
PubMed1978

[Double-blind study on the anti-convulsive effect of phenobarbital and valproate in the Lennox syndrome].

In a double-blind crossover trial valproate was compared with phenobarbital with regard to anticonvulsive activity and tolerance in 17 epileptic children (mean age 55 +/- 26 months) with Lennox syndrome. Valproate in association with a phenobarbital dose reduced by about 40% proved to be to a statistically significant degree more active against epileptic seizures than phenobarbital alone. No difference in the effect on the EEG tracings was observed. Valproate appeared to be somewhat more active than phenobarbital with regard to behaviour, but the difference was not significant. Tolerance to both products was equally good.

Benzodiazepines↗
PubMed1978

Influence of a GABA transaminase inhibitor on central nervous system oxygen toxicity.

A decrease in brain GABA concentration has been implied as the cause of convulsions induced by hyperbaric oxygen (HOP). We therefore examined the influence of sodium valproate, an anticonvulsant and GABA transaminase inhibitor on HOP-induced convulsions in rats. The mean latency of occurrence of the first electrical discharge in the ECoG and the appearance of the first clinical seizure in awake chronically implanted rats was unchanged by administration of sodium valproate prior to HOP exposure. We conclude that either the sodium valproate inhibition of GABA removal is insufficient to compensate for HOP inhibition of its production, or else that GABA concentration changes are not causally related to HOP-induced seizures.

4-Aminobutyrate Transaminase↗
PubMed1987

Normalization of lipoprotein lipase and hepatic lipase by gemfibrozil results in correction of lipoprotein abnormalities in chronic renal failure.

Eighteen patients with chronic renal failure (serum creatinine 173-756 mumol/l) and hyperlipidemia were treated with gemfibrozil (1200 mg/day). The drug caused a significant improvement of the dyslipidemia within one week and the effect was progressive during the 28 weeks of treatment. Very-low-density lipoprotein triglycerides and very-low-density lipoprotein cholesterol decreased by about 50% and high-density lipoprotein cholesterol increased by 30%. The lipoprotein changes occurred simultaneously with a significant activation to normal levels of postheparin plasma lipoprotein and hepatic lipases. Opposite effects were observed when gemfibrozil was discontinued and the patients were given placebo. No major harmful effects were observed.

Adult↗
PubMed1987

Protein origin of the volatile fatty acids isobutyrate and isovalerate in human stool.

Normal human stool contains five commonly recognized volatile fatty acids, of which three (acetate, propionate, and butyrate) are the product of carbohydrate degradation. We investigated whether the remaining two volatile fatty acids, isobutyrate and isovalerate, are produced by degradation of amino acids. Stools from six healthy subjects were incubated with albumin, valine, leucine, tryptophan, phenylalanine, glucose, or sucrose under atmospheres containing oxygen in the range of 0% to 5%. Isobutyrate was produced only from albumin and valine, and isovalerate was produced only from albumin and leucine. Glucose- and sucrose-containing incubates produced only acetate, propionate, and butyrate. The rate of production for each of the volatile fatty acids was constant over the various oxygen concentrations tested. We conclude that isobutyrate and isovalerate in stool are formed from valine and leucine degradation respectively. Quantitation of individual fecal volatile fatty acid excretions may reflect intracolonic degradation of protein and carbohydrate.

Albumins↗
PubMed1985

Gemfibrozil therapy in primary hypertriglyceridemia associated with coronary heart disease. Effects on metabolism of low-density lipoproteins.

Certain primary hypertriglyceridemias cause abnormalities in lipoproteins that seemingly predispose patients to coronary heart disease. We examined metabolism of low-density lipoproteins (LDL) in 11 men with both hypertriglyceridemia and coronary heart disease and compared them with that of controls. The LDL turnover was measured during placebo and gemfibrozil therapy. With placebo, LDL-cholesterol level usually was normal, but production and fractional clearance of LDL were high. The LDL composition also was abnormal. Gemfibrozil reduced triglycerides, lowered production and fractional clearance of LDL, and normalized LDL composition. The LDL-cholesterol level usually rose, but generally not to abnormally high levels. Therefore, normalization of LDL metabolism and marked reduction of triglycerides by gemfibrozil suggest benefit to hypertriglyceridemic patients who are at high risk for coronary heart disease. However, when LDL-cholesterol level rises excessively, gemfibrozil may not be sufficient therapy.

Adult↗
PubMed1979

The effect of gemfibrozil on serum lipids in diabetic patients.

The effect of gemfibrozil, a new hypolipidaemic compound, on serum lipids, lipoproteins and ophthalmic signs was studied in 20 diabetics during a 28 week trial. Ten of the patients were taking oral hypoglycaemic agents and another ten insulin. Genfibrozil elevated the proportion of alpha-lipoproteins (HDL) (P less than 0.005) in patients on oral agents to the same level as in those using insulin, who experienced no change in HDL. The pre-beta-lipoprotein proportion (VLDL) decreased (P less than 0.001) along with the serum triglyceride level in patients on oral agents only. The proportion of beta-lipoproteins (LDL) remained unchanged in both groups. The serum cholesterol and total lipid levels decreased significantly whether the patients were on oral treatment or insulin. The gemfibrozil was well tolerated. A minor increase in diabetic therapy was made in 9 patients in order to control the blood sugar levels. The ophthalmic signs were generally unchanged.

Administration, Oral↗
PubMed1977

[The treatment of primary generalized epilepsies with dipropyl acetate (DPA)].

79 patients with primary generalized epilepsies have been treated with DPA in a medium dosage of 51 mg/kg bodyweight/day, range 14 to 125 mg/kg/day, for a medium time of 22 months, range 2 to 49 months. 51 children out of this group had been treated previously and were therapy resistant to other medications. 27 children got DPA for their first medication. 34 patients were treated with DPA as a single drug, 45 were treated in combination with other medications. Therapeutic success was found to be remarkable good in impulsive petit mal (n = 4, all patients without any more seizures), in absences (n = 52, complete success in 84%), and in primary generalized grand mal seizures with spike-waves in the EEG alone or in combination with petit mal (n = 30, 87% success). However, centrencephalic myoclonic-astatic seizures (n = 17, no more seizures in 35%) were influenced significantly less. Side effects were rarely seen, mostly they could be observed in those patients treated with DPA and another medication. Side effects never induced interruption of treatment with DPA.

Adolescent↗