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B Begaud

Publications and source records attributed to B Begaud.

At least 37 records · Page 2Linked to original sources
PubMed1991

Random models for margins of a 2 x 2 contingency table and application to pharmacovigilance.

The identification of new adverse drug reactions is often tricky. For a given case, the relationship between drug exposure and symptom occurrence is usually questionable. It could be investigated statistically from a series of drug-event association cases with an independence test between the two variables. Analysing the related 2 x 2 contingency table obviously requires knowledge of its margins. However this information is often not available. We develop a calculation of the P-value by choosing some random models for the unknown margins. Under the hypothesis of independence, a negative binomial distribution for the frequency of the drug-event association cell is obtained, exactly or approximately. This method allows investigation of the causal relationship when some parameters, as incidence of the symptom in the population, are uncertain. An example is presented.

Anticoagulants↗
PubMed1991

Pharmacokinetics and protein binding of cefpiramide in patients with alcoholic cirrhosis.

The pharmacokinetics of cefpiramide, a new cephalosporin, were investigated after a single 1 gm intravenous injection in 11 patients with alcoholic cirrhosis and compared with those of 11 healthy subjects. In patients with cirrhosis the plasma elimination half-life was three times longer than that in normal subjects. The total plasma clearance was decreased significantly (p less than 0.001): 12.3 +/- 6.5 ml/min in patients and 25.6 +/- 4.6 ml/min in healthy volunteers, respectively. The urinary excretion of unchanged drug (percent of intravenous dose) for patients (69.8% +/- 29.9%) was statistically higher (p less than 0.01) than that for subjects (16.2% +/- 3.9%). The renal elimination became increasingly important with hepatic impairment. Protein binding of cefpiramide was reduced significantly in the group with cirrhosis. The average unbound fraction was 10.4% +/- 9.5% in patients with cirrhosis and 1.9% +/- 0.3% in normal subjects (p less than 0.01). Because the rate of elimination from plasma in patients is slower, the dosage regimen of cefpiramide would probably be modified in cirrhosis.

Adult↗
PubMed1987

Effect of aluminum phosphate on the bioavailability of ranitidine.

The effect of aluminum phosphate on the bioavailability of ranitidine has been investigated in 10 young, healthy volunteers. Following a random cross over design, each subject took at a 1 week interval 150 mg ranitidine alone or with 11 g aluminum phosphate. Plasma and urine ranitidine levels were measured by HPLC. The antacid reduced both the maximum plasma ranitidine concentration by 40% and the area under the curve by 30%. Elimination of ranitidine was not changed. The results indicate that aluminum phosphate significantly diminished the bioavailability of ranitidine.

Adult↗
PubMed1987

Antihypertensive effects of mesulergine: further evidence for a peripheral site of action of dopamine agonists.

The cardiovascular effects of mesulergine were studied in anesthetized dogs. Intravenous (IV) administration (0.3 mg/kg) significantly decreased blood pressure in neurogenic hypertensive dogs without any change in heart rate. This effect was completely antagonized by IV administration of domperidone (0.5 mg/kg). Intracisternal administration of mesulergine (0.03, 0.3 and 3 mg/kg) did not produce any change in blood pressure. However, with the highest dose we observed a significant rise in heart rate during the first 2 min (which was probably nonspecific). These results suggest that mesulergine lowers blood pressure in sinoaortic-denervated dogs by means of a peripheral mechanism probably involving DA2 receptors. The findings confirm the potential interest of dopamine-receptor agonists as future antihypertensive agents.

Animals↗
PubMed1986

Computerized comparison of six adverse drug reaction assessment procedures.

Several standardized assessment procedures are currently used in the evaluation of adverse drug reactions (ADRs). Disagreement in rating ADRs can result from between-raters variability and between-methods differences in weighting the evidence. We eliminated between-raters variability by computer simulation of 1134 ADRs (including all the possible combinations of criteria currently used) and by automatic rating using different algorithms adapted from six published methods. Percentage agreement (Po) and weighted kappa test (kappa w) between pairs of methods are always better than with randomized scores, but the strength of agreement is only moderate (0.26 less than Po less than 0.59; 0.14 less than kappa w less than 0.51). The weightings of criteria are evaluated in terms of sensitivity, specificity, and predictive values. Criteria are neither sensitive (0.41 less than Se less than 0.70) nor specific (0.18 less than Sp less than 0.63) and have poor predictive values. Disagreements on weightings are considerable for three major criteria: timing of event, dechallenge, and alternative etiologic candidates. We discuss some ways of improving reliability of ADR diagnosis.

Computers↗
PubMed1986

Effects of hydralazine on regional blood flow in conscious dogs.

This study was designed to assess the effects of hydralazine administered p.o. on regional circulation, including the carotid, coronary and renal arteries. Hydralazine in doses of 0.5, 1 and 5 mg/kg (p.o., n = 5) increased coronary blood flow by 9 +/- 4, 15 +/- 4 and 18 +/- 3 ml/min (P less than .05), respectively, and renal blood flow by 17 +/- 7, 26 +/- 12, 36 +/- 10 ml/min (P less than .05), respectively, but had no effects on carotid blood flow in conscious, normotensive dogs. The increase in coronary blood flow was correlated linearly with the rate pressure product (r = 0.581, P less than .05). After ganglionic blockade using chlorisondamine (2 mg/kg i.v.), hydralazine in a dose of 1 mg/kg (p.o., n = 4) increased renal blood flow by 45 +/- 6 ml/min (P less than .05), whereas mean arterial pressure, cardiac output, heart rate and coronary blood flow remained essentially unchanged. The increase in renal blood flow produced by hydralazine (1 mg/kg p.o., n = 6) was prevented by pretreatment with a cyclooxygenase inhibitor, indomethacin (2 mg/kg, i.v.). In vitro, hydralazine failed to relax segments of carotid, coronary and renal arteries. Our data indicate that hydralazine is a direct and preferential renal vasodilator. It produces an indirect coronary vasodilation related to an increase in myocardial oxygen demand. Its effect on renal circulation appears to be dependent on the prostaglandin system and is related mainly to a relaxation of arteriolar resistant vessels.

Animals↗
PubMed1985

Effect of two antacids on the bioavailability of paracetamol.

The effect of two antacids on the bioavailability of paracetamol has been investigated in 12 young healthy volunteers. Following a random cross over design, each subject swallowed, on three separate occasions, one weak apart, 500 mg paracetamol alone, or together with two different aluminium hydroxide, magnesium hydroxide preparations (Dimalan and Maalox). Plasma paracetamol levels were measured by HPLC. The bioavailability of paracetamol was not altered by either antacid, but they both delayed the time to peak plasma concentration (0.85 h; 1.43 h; 1.25 h, without antacid, with Dimalan and with Maalox respectively). The peak plasma concentration was not affected by concurrent antacid administration.

Acetaminophen↗
PubMed1984

Effect of aluminium phosphate on the bioavailability of cimetidine and prednisolone.

Ten fasting subjects received 200 mg cimetidine orally either with water or 11 g aluminium phosphate mixture in a randomized, single dose, two-way cross-over study. Blood samples were taken for 12 h and urine was collected for 24 h. Cimetidine in plasma and urine was analysed by HPLC. There were no significant differences between the treatments with respect to peak plasma concentration, time to peak plasma concentration, area under the plasma concentration-time curve, and urinary excretion. In 12 healthy subjects the absorption of prednisolone was investigated when given alone and together with 11 g aluminium phosphate. Blood samples were taken over 16 h and prednisolone in plasma was analysed by HPLC. There were no significant differences in the values of area under curve (AUC), Cmax and tmax. The results indicate that aluminium phosphate does not reduce the bioavailability of cimetidine and prednisolone.

Adult↗
PubMed1984

Standardized assessment of adverse drug reactions: the method used in France. Special workshop--clinical.

The method used in France since 1977 for assessing adverse drug reaction (ADRs) is based on a three-stage process: assessment of three chronological criteria (challenge, dechallenge, and rechallenge); assessment of clinical and biological findings; and a combination of chronological and symptomatological assessments to obtain a 3-degree global score (1: doubtful, 2: possible, 3: probable). Bibliographical data (previously reported or unreported ADR) are assessed quite separately; thus, the method has a good sensitivity for detecting new ADRs.

Drug-Related Side Effects and Adverse Reactions↗
PubMed1982

[Imputability of drug side effects].

By imputability it is meant the assessment of the probable responsability of a drug in the development of undesirable effect. Its principle is based on the evaluation of some criteria derived from observation (intrinsic imputability) or relevant literature (extrinsic imputability). Around ten imputability methods have so far been reported; although they are not comparable, personnel differences in evaluation may be avoided.

Drug-Related Side Effects and Adverse Reactions↗
PubMedDate not supplied

[Psychotic disorders linked to the inhibition of benzodiazepine catabolism].

Five clinical cases of interaction between benzodiazepines on one hand and erythromycin, troleandomycin, josamycin and cimetidine on the other hand have been analyzed. These interactions resulted in severe disorders of behaviour, amnesia (including amnesia-automatism syndrome in one case), disturbances of consciousness and withdrawal syndrome. These disorders were consecutive to inhibition of the hepatic cytochrome P-450 system. Practical means of avoiding this risk consists in limiting such drug combinations, reducing benzodiazepine dosage and, if a combined treatment is necessary, using by preference either benzodiazepines degraded by conjugation instead of oxidation, or macrolides, or anti-H2 compounds with reduced inhibitory effect on microsomes.

Adult↗
PubMedDate not supplied

[Cost of hospitalizations for adverse drug effects].

The French network of Regional Pharmacovigilance Centres evaluated in 1997 the prevalence of adverse effects of drugs (AED). In 1998, and again with the support of the French Drug Agency, in collaboration with the company CEMKA for economic evaluations, the incidence of AED-related hospitalizations in the medical department of French public hospitals was studied. The evaluation was performed over 14 consecutive days in 62 hospital departments, which were selected randomly. The total number of 3137 patients were hospitalized for a mean duration of 9 days and they were using a mean number of six different drugs. Taking into account the number of about 4 million patients admitted per year in the hospitals represented, it was estimated that the total number of AED-related hospitalizations amounts to about 130,000 annually (CI95%: 100,916-156,620). Using established cost calculations for hospitalized days (AP-HP, results of 1996) the mean cost for an AED-related hospitalization was estimated to be about FF16,000.

Adult↗