The pharmacokinetics of valproic acid (VPA) was investigated in six healthy volunteers. This was done by monitoring total and free (unbound) valproic acid levels in the serum, and the amount of one of its metabolites, VPA glucuronide, in the urine as a function of time, after a single dose administration of the parent drug. VPA half-life calculated from the urine data of the metabolite was shorter than the half-life calculated from the blood data. About 15 to 20 per cent of the administered oral dose of VPA was excreted in the urine as VPA glucuronide. The average free fraction of VPA obtained in this study, by using the EMIT technique, ranged from 1.5 to 11.5 per cent with a mean value of 4.9 per cent.

Adult↗

PubMedDate not supplied

Pharmacokinetic evaluation of novel sustained-release dosage forms of valproic acid in humans.

Five new sustained-release dosage forms of valproic acid (VPA) were developed. The new sustained-release formulations were administered to six healthy subjects for comparison with a standard tablet and an i.v. preparation of the drug. Three of the formulations exhibited a more prolonged and uniform absorption rate and yielded more sustained serum levels after ingestion. These three formulations maintained serum therapeutic levels of VPA for 24 h after a single oral administration of 1 g, and were bioequivalent to a marketed standard tablet of VPA. The absorption profile of the various oral formulations was analysed pharmacokinetically, using the Loo-Riegelman procedure.

Administration, Oral↗

PubMedDate not supplied

Significance in neonatal myasthenia gravis of inhibitory effect of amniotic fluid on binding of antibodies to acetylcholine receptor.

The effect of amniotic fluid on the binding of anti-acetylcholine receptor (anti-AChR) antibodies from myasthenia gravis (MG) patients to AChR preparations was examined by radioimmunoassay using 125I-labelled alpha-bungarotoxin. Human amniotic fluid from healthy women in their second trimester inhibited the in-vitro interaction between antibody and antigen. This finding suggests that during pregnancy there is a similar inhibitory effect in MG on the in-vivo binding of maternal anti-AChR antibodies, transferred through the placenta, to AChR at the fetal neuromuscular junction. The presence of feto-placental inhibitory factors may explain the development of transitory muscular weakness only after birth and only in the minority of the babies born to myasthenic mothers.

Acetylcholine↗

PubMedDate not supplied

Suppressive effect of pregnancy on the development of experimental allergic encephalomyelitis in rabbits.

In the present study we have investigated the influence of pregnancy on the induction and development of experimental autoimmune encephalomyelitis (EAE) in rabbits in relation to the time of gestation. Randomly bred rabbits were immunized with encephalitogenic bovine brain homogenate in complete Freund's adjuvant before or during pregnancy. The appearance of EAE was delayed and occurred only after delivery, abortion, or fetal resorption. The incidence of the disease was lower and the duration longer. The levels of antibodies to myelin basic protein, an autoantigen of EAE, as measured by solid phase radioimmunoassay, were lower in the pregnant rabbits as compared to the nonpregnant animals. The suppressive influence of pregnancy on the induction and the development of EAE confirms previous reports demonstrating amelioration of autoimmune diseases and other immunological reactions during the second half of human pregnancy. This effect might be partially attributed to the increased level of alpha-fetoprotein (AFP) and/or other pregnancy-associated factors in maternal serum.

Animals↗

PubMedDate not supplied

Absence of neural responses following suppression of the immune response by cyclophosphamide.

Injection of sheep red blood cells (SRBC) as an antigenic stimulus, causes significant increases (up to 300%) in multiunit neural activity in the preoptic area/anterior hypothalamus of conscious rats. This increase occurs on the fifth or sixth day after immunization, at the time of first appearance of circulating antibodies at a serum titer of 1:32, increasing to 1:128 by day 10 following sensitization. Treatment with the immunosuppressive drug cyclophoshamide was able to prevent both antibody production and the expected increases in electrical activity in 5 of 6 rats; the one remaining animal showed a low level of circulating anti-SRBC antibodies on day 10 (1:32) and also, a small increase (36%) in neural activity at the expected time. These results provide further evidence that activation of the immune system is able to alter neuronal activity in an area of the brain important in the regulation of both neuroendocrine and neuroimmunomodulatory mechanisms, and that such activity is probably due to soluble secretory products released from components of the immune system.

Animals↗

PubMedDate not supplied

Neural responses to antigenic challenges and immunomodulatory factors.

In studies designed to examine the effects of the immune system, recordings of multi-unit electrical activity (MUA) in the central nervous system were made in the preoptic area/anterior hypothalamus (POA/AH) and paraventricular nucleus (PVN) of rats, following sheep red blood cell (SRBC) immunization. Peak increases in POA/AH MUA were observed on the fifth day following SRBC sensitization, the day on which serum antibodies were first detected. A significant increase in paraventricular nucleus (PVN) MUA was also observed on the sixth day. These changes in POA/AH and PVN MUA were found to be associated with increased plasma corticosterone levels on day 8. Induction of a second immune response to SRBC evoked a POA/AH MUA increase of extended duration but reduced amplitude, while administration of the immunosuppressive drug, cyclophosphamide, prevented both antibody generation and any increases in POA/AH MUA. These data suggest that activation of the immune system may provide signals, in the form of chemical messengers, which are able to alter neural activity in some regions of the brain that are important in neuroendocrine regulatory mechanisms. Accordingly, intracerebroventricular injections of thymic humoral factor or alpha-interferon decreased POA/AH MUA, increased EEG synchronization, and decreased plasma levels of corticosterone. Histamine and interleukin 1 did not alter POA/AH MUA but decreased EEG synchronization and increased plasma levels of corticosterone.

Animals↗

PubMedDate not supplied

Neurophysiological changes in the brain following central administration of immunomodulatory factors.

Explore the source record for details and available documents.

Animals↗