Search PubMed⌕ Search

Biomedical subjects

B F Bourgeois

Publications and source records attributed to B F Bourgeois.

49 records · Page 3Linked to original sources
PubMed1983

Intelligence in epilepsy: a prospective study in children.

A prospective study tested the stability of the IQ in children with seizure disorders. Seventy-two children with epilepsy underwent psychological evaluations within two weeks of initial diagnosis and yearly thereafter for an average of 4 years. Forty-five of the patients also had a nonepileptic sib evaluated in parallel. The mean IQ for all the children with epilepsy was 99.7 (+/- 20.2, standard deviation) at the time of the initial test, not significantly different from the siblings. This score did not change appreciably with time. Eight of the 72 epileptic patients (11.1%), however, had a persistent decrease in IQ of 10 points or more. These patients had a higher incidence of drug levels in the toxic range (p less than 0.001), their epilepsy was more difficult to control (p less 0.005), and their seizures began at an earlier age (p less than 0.05). Discriminant analysis is revealed that the number of drugs to which the patient became toxic and the age at seizure onset were the two best predictors of ultimate IQ. These two predictors correctly classified 71% of all patients as to whether their IQ would drop by 10 or more points during the test period, remain within 10 points of the initial test score, or increase by more than 10 points. Total number of seizures and seizure control were less good predictors, according to this method of analysis. The findings suggest that, in younger children in particular, total seizure control should not be achieved at the price of repeated episodes of drug toxicity.

Adolescent↗
PubMed1983

Potentiation of the antiepileptic activity of phenobarbital by nicotinamide.

Nicotinamide is a ligand of the benzodiazepine receptor and has been reported to have anticonvulsant activity. In addition, our previous clinical experience has raised the possibility that it may also potentiate the action of barbiturates. Therefore, we have examined the anticonvulsant activity and neurotoxicity of nicotinamide alone and in combination with phenobarbital in mice. Nicotinamide had its maximal anticonvulsant effect 15 min and its maximal sedative effect 45 min after intraperitoneal injection. At 15 min, the median effective dose was 586.5 mg/kg against bicuculline and 2,019 mg/kg against pentylenetetrazol. Nicotinamide was ineffective against maximal electroshock. It had a sedative effect, with a median toxic dose of 874.8 mg/kg by the Rotorod Toxicity Test at 45 min. At doses that were ineffective by themselves (0.01 effective dose) nicotinamide potentiated the anticonvulsant activity of phenobarbital against bicuculline and pentylenetetrazol, but the toxicity was not potentiated and therefore the therapeutic index of phenobarbital was improved by nicotinamide. These results suggest that nicotinamide may be useful as a therapeutic adjunct for the treatment of epilepsy with phenobarbital or primidone.

Animals↗
PubMed1983

Phenytoin elimination in newborns.

We measured the apparent half-life (t50%) of phenytoin (PHT) 30 times in 16 infants (aged 2 to 36 days) who had seizures. During the first week of life, the t50%s ranged from 6 to 140 hours. After the first week, the concentration dependence of PHT elimination was demonstrated; the t50% was related to the initial concentration (Ci). The t50% also decreased with postnatal age. Controlling for a Ci of 18 mg per liter, the average t50% decreased threefold between the first (57.3 +/- 48.2 hours) and fourth weeks (19.7 +/- 1.31). In newborns, both age-related changes and the concentration dependence of PHT elimination can cause PHT levels to decrease when constant doses are given.

Age Factors↗
PubMed1983

Primidone, phenobarbital, and PEMA: I. Seizure protection, neurotoxicity, and therapeutic index of individual compounds in mice.

Neurotoxicity and protection against maximal electroshock and Metrazol seizures from primidone (PRM), phenobarbital (PB), and phenylethylmalonamide (PEMA) were determined in mice for each drug separately and expressed in terms of brain concentrations. Compared with PB, PEMA was 16 times less potent against electroshock and Metrazol seizures but only 8 times less toxic. Primidone was markedly less neurotoxic than PB and equally potent against electroshock, but PRM had no effect against Metrazol or bicuculline. PRM is a relatively nontoxic anticonvulsant with a different action than PB, and PEMA is both a weak and a relatively toxic anticonvulsant.

Animals↗
PubMed1983

Primidone, phenobarbital, and PEMA: II. Seizure protection, neurotoxicity, and therapeutic index of varying combinations in mice.

Neurotoxicity and protection against maximal electroshock (MES) and pentylenetrazol (Metrazol) seizures were determined in mice for various combinations of primidone (PRM), phenobarbital (PB), and phenylethylmalonamide (PEMA). The results suggest that PRM and PB together are superior to either one alone in terms of spectrum of activity and relative toxicity. The protection against Metrazol and the toxicity of PB are both potentiated by PEMA at low concentrations. PEMA also potentiates the toxicity of combined PRM plus PB, without altering their protection against MES, thus lowering their therapeutic index. We conclude that PRM and PB together have an advantage over PB alone, especially when their brain concentration ratio is at or above 1 and PEMA concentrations are low. These conditions are usually not present at steady state in patients treated with PRM.

Animals↗
PubMed1982

Interactions between primidone, carbamazepine, and nicotinamide.

The effect of nicotinamide on the conversion of primidone to phenobarbital was studied in mice and in three epileptic patients. In mice, 200 mg per kilogram of nicotinamide increased the half-life of primidone by 47.6%, and the conversion to phenobarbital and phenylethylmalonamide was decreased by 32.4% and 14.5%, respectively. Nicotinamide also decreased the conversion of primidone to phenobarbital in patients. The dose of nicotinamide correlated directly with the primidone-phenobarbital ratio (r = 0.861, p less than 0.01). Nicotinamide also increased carbamazepine levels in two patients treated with this drug. The data demonstrate that nicotinamide inhibits metabolism of primidone in mice and metabolism of primidone and carbamazepine in humans. This probably occurs by inhibition of cytochrome P-450 by nicotinamide.

Animals↗
PubMed1979

Effects of cardiac surgery on renal function in children.

In order to determine whether cardiac surgery with cardiopulmonary bypass (CPB) affects renal function in children, glomerular filtration rate (GFR and renal plasma flow (RPF) were determined preoperatively and on the second postoperative day by a single-injection, urineless technique in a randomly selected group of 10 children. The GFR was 126.7 +/- 6.8 ml. per minute per 1.73 sq. M. (mean +/- S.E.M.) before the operation and 127.4 +/- 16.2 on the second postoperative day (p = 0.95). The RPF was 541.7 +/- 80.6 ml. per minute per 1.73 sq. M. preoperatively and 536.0 +/- 82.1 on the second postoperative day (p = 0.8 to 0.9). The results in this group of 10 children indicate that renal function is not markedly altered 2 days after cardiac surgery with CPB and deep hypothermia with circulatory arrest. The study also revealed a falsely decreased creatinine clearance. This was due to an increase in postoperative plasma creatinine values, probably related to an increase in plasma noncreatinine chromogens.

Acute Kidney Injury↗
PubMedDate not supplied

New antiepileptic drugs in children: which ones for which seizures?

Until 1993, carbamazepine (CBZ), phenytoin (PHT), phenobarbital (PB), and valproate (VPA) accounted for the great majority of the prescriptions written for the treatment of epilepsy. Since 1993, five antiepileptic drugs (AEDs) have been released in the United States, and at least three additional drugs are expected to be released by the end of the year 2000. As a group, these newer drugs differ from the established drugs in terms of their pharmacokinetics, interaction potential, and adverse effects. In addition, any one of the newer drugs may achieve seizure control in situations in which an established drug had not. The newer drugs certainly represent a welcome addition to the existing options for the treatment of epilepsy in children. However, the availability of several new AEDs represents a therapeutic dilemma for the clinician because optimal use of these drugs has not yet been established. This is particularly true in children because (i) newer drugs are often studied less frequently in children, (ii) pharmacokinetics in children differ from those in adults, (iii) children may have different adverse effects, and (iv) children have a broader spectrum of various seizure types and epilepsy syndromes. In the first part of this review, the clinical pharmacology of the currently available newer AEDs is discussed individually, with special emphasis on data in children. In particular, pharmacokinetics, interactions, dosage and titration, efficacy spectrum, and adverse effect profile is discussed for each drug. In the second part, an attempt is made to determine the place for the newer drugs in the treatment of the different pediatric seizures and epilepsy syndromes.

Anticonvulsants↗
PubMedDate not supplied

Pharmacokinetics of R-enantiomeric normephenytoin during chronic administration in epileptic patients.

Stereoselective metabolism has been demonstrated for mephenytoin (MHT), R-MHT being demethylated to the pharmacologically active metabolite 5-phenyl-5-ethylhydantoin (PEH; nirvanol), and S-MHT undergoing aromatic hydroxylation to 4-OH-MHT, with formation of an intermediate arene oxide metabolite. PEH is responsible for the therapeutic effect, whereas 4-OH-MHT is rapidly eliminated by the kidneys. The arene oxide metabolite may have implications in MHT toxicity. The metabolism of PEH is also stereospecific. In the present study, the R-enantiomer of PEH (R-PEH; R-normephenytoin) was administered chronically during 8 weeks to four epileptic patients, as a single dose every 3 days. The half-lives of R-PEH ranged from 77.7 to 175.8 h, and correlated closely with the creatinine clearance. Mean urinary recovery of R-PEH was 86.6% of the dose at steady state, with 4-OH-PEH accounting for only 5%. This indicates that, unlike Nirvanol (a racemic mixture of R- and S-PEH), R-PEH is only minimally metabolized, even after several weeks of treatment and despite potential enzymatic autoinduction and heteroinduction by other antiepileptic drugs. Complete blood counts and liver function tests revealed no alteration, and no other adverse effects were noted. If arene oxide intermediate metabolites are indeed involved in the toxicity of MHT and nirvanol, R-PEH may represent a safer alternative.

Adult↗
PubMedDate not supplied

Combined administration of carbamazepine and phenobarbital: effect on anticonvulsant activity and neurotoxicity.

Despite the trend towards single drug therapy of epilepsy, patients resistant to monotherapy are commonly treated with more than one antiepileptic drug. As part of an investigation on the experimental background for antiepileptic drug combinations, the effect of the pharmacodynamic interactions between carbamazepine and phenobarbital on the toxicity/efficacy ratio was studied in mice. All results were expressed in terms of drug concentrations in the brain to exclude possible pharmacokinetic interactions from the analysis. A purely additive interaction was found for the anticonvulsant as well as for the neurotoxic effect of the drugs. The combination of carbamazepine and phenobarbital has therefore no advantage over each drug alone in this model. Based on these and previous results, there is no experimental evidence in favor of any combination between the four main drugs against partial seizures, i.e., carbamazepine, phenytoin, phenobarbital, and primidone.

Animals↗
PubMedDate not supplied

Rapid reversibility of autoinduction of carbamazepine metabolism after temporary discontinuation.

Patients in whom carbamazepine (CBZ) monotherapy is discontinued for preoperative EEG/video monitoring often display toxicity if their previous maintenance dosage is resumed, even after a few days without CBZ. To determine whether this is due to rapid reversibility of autoinduction of CBZ metabolism, single-dose studies of CBZ pharmacokinetics were performed before and after discontinuation for monitoring in 6 adults receiving CBZ monotherapy. The CBZ-free period was 5.7 +/- 1.1 days (mean +/- SD). The pharmacokinetic parameters of CBZ before and after discontinuation were volume of distribution (Vd) 1.28 +/- 0.29 versus 1.22 +/- 0.331/kg (NS), elimination half-life (t1/2) 13.7 +/- 1.67 versus 22.2 +/- 2.36 h (p < 0.001), and clearance (Cl) 1.54 +/- 0.39 versus 0.92 +/- 0.32 L/kg/day (p = 0.012). Assuming that deinduction is a first-order process, a deinduction t1/2 of 3.84 days was obtained by log linear regression analysis. We showed that after CBZ discontinuation half of the enzymatic autoinduction is already lost after 3.84 days, indicating very rapid deinduction. Our results also provide the necessary information to predict clearance and appropriate dosage reduction for CBZ at time of reintroduction.

Administration, Oral↗