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Elisabeth Autret-Leca

Publications and source records attributed to Elisabeth Autret-Leca.

12 recordsLinked to original sources
PubMed2005

Bayesian estimation of cyclosporin exposure for routine therapeutic drug monitoring in kidney transplant patients.

AIMS: AUC-based monitoring of cyclosporin A (CsA) is useful to optimize dose adaptation in difficult cases. We developed a population pharmacokinetic model to describe dose-exposure relationships for CsA in renal transplant patients and applied it to the Bayesian estimation of AUCs using three blood concentrations. METHODS: A total of 84 renal graft recipients treated with CsA microemulsion were included in this study. Population pharmacokinetic analysis was conducted using NONMEM. A two-compartment model with zero-order absorption and a lag time best described the data. Bayesian estimation was based on CsA blood concentrations measured before dosing and 1 h and 2 h post dose. Predictive performance was evaluated using a cross-validation approach. Estimated AUCs were compared with AUCs calculated by the trapezoidal method. The Bayesian approach was also applied to an independent group of eight patients exhibiting unusual pharmacokinetic profiles. RESULTS: Mean population pharmacokinetic parameters were apparent clearance 30 l h(-1), apparent volume of distribution 79.8 l, duration of absorption 52 min, absorption lag time 7 min. No significant relationships were found between any of the pharmacokinetic parameters and individual characteristics. A good correlation was obtained between Bayesian-estimated and experimental AUCs, with a mean prediction error of 2.8% (95% CI [-0.6, 6.2]) and an accuracy of 13.1% (95% CI [7.5, 17.2]). A good correlation was also obtained in the eight patients with unusual pharmacokinetic profiles (r(2) = 0.96, P < 0.01). CONCLUSIONS: Our Bayesian approach enabled a good estimation of CsA exposure in a population of patients with variable pharmacokinetic profiles, showing its usefulness for routine AUC-based therapeutic drug monitoring.

Adult↗
PubMed2005

Pediatric intravenous paracetamol (propacetamol) pharmacokinetics: a population analysis.

BACKGROUND: The aim of this study was to describe propacetamol pharmacokinetics in children in order to predict concentrations after a standard dosing regimen of propacetamol 30 mg x kg(-1) (15 mg x kg(-1) paracetamol) 6 h. METHODS: A population pharmacokinetic analysis of paracetamol time-concentration profiles (846 observations) from 144 children [postconception age (PCA) 27 weeks-14 years] was undertaken using nonlinear mixed effects models (NONMEM). These data were taken from seven separate studies involving children given intravenous propacetamol. Time-concentration profiles (503 observations) from a further 86 children (PCA: 37 weeks-14 years) given paracetamol elixir orally were included in the analysis to assess relative bioavailability of intravenous propacetamol. RESULTS: A three-compartment (depot, central and peripheral) linear disposition model fitted data better than a two-compartment (depot and central) model. Population parameter estimates (between subject variability, %) were central volume (V2/F(oral)) 24 (55%) l x 70 kg(-1), peripheral volume of distribution (V3/F(oral)) 30 (32%) l x 70 kg(-1), clearance (CL/F(oral)) 16 (40%) l x h(-1) x 70 kg(-1) and intercompartment clearance (Q/F(oral)) 55 (116%) l x h(-1) x 70 kg(-1). Clearance increased from 27 weeks PCA (1.87 l x h(-1) 70 kg(-1)) to reach 84% of the mature value by 1 year of age (standardized to a 70 kg person using allometric '1/4 power' models). Peripheral volume of distribution decreased from 27 weeks PCA (45.0 l x 70 kg(-1)) to reach 110% of its mature value by 6 months of age. Central volume of distribution and intercompartment clearance did not change with age. Between occasions variability for the peripheral volume of distribution (V3/F(oral)) and clearance (CL/F(oral)) were 18.5 and 19.3%, respectively. A rate constant representing hydrolysis of propacetamol to paracetamol (K(a) 96 h(-1)) was size related, but not age related. The relative bioavailability of intravenous propacetamol compared with an oral elixir was 0.5. CONCLUSIONS: A mean paracetamol serum concentration of 10 mg x l(-1) is achieved in children 2-15 years given a standard dose of propacetamol 30 mg x kg(-1) 6 h. This concentration in the effect compartment is associated with a pain reduction of 2.6/10 after tonsillectomy and provides satisfactory analgesia for mild to moderate pain. Clearance is reduced in children less than 1 year of age and the target concentration of 10 mg x l(-1) may be achieved by scaling this standard dose regimen using predicted clearance in this younger age group.

Acetaminophen↗
PubMed2004

[Vaccines pharmacovigilance].

The pharmacovigilance of vaccines has the particularity of concerning medications with a preventative target, used in healthy subjects, who are often young. Their individual benefit is deferred and unknown, whereas their risk is immediate. Certain undesirable effects are linked to the antigen of live attenuated vaccines (post-MMR lymphocytic meningitis). Other non-specific effects are linked to other different components of the vaccines (macrophage and aluminium myofasciitis). Undesirable events susceptible to being due to the vaccination are identified and managed according to standardised procedures of pharmacovigilance, that is to say, based on "spontaneous notification", generation of an alert, confirmed or not by studies of pharmaco-epidemiology. The studies of pharmaco-epidemiology: have made evident oedematous reactions with cyanosis or purpura, with the vaccines containing the Haemophilus b valence, and the absence of an association with sudden death of the newborn; have excluded the existence of an elevated risk of demyelinisation or auto-immune disease associated with vaccination against hepatitis B, without being able to exclude a slight risk; go against the finding of an association between Crohn's disease and/or autisim and the MMR vaccination. Only their frequently encountered undesirable effects are well identified at the moment of commercialisation. Post-marketing surveillance of vaccines (declaration to the regional pharmacovigilance centres) allow the detection of possible rare and serious effects and the evaluation of the real vaccination risk. Thus it must be intensive and systematic.

Adverse Drug Reaction Reporting Systems↗
PubMed2003

A general overview of the use of ibuprofen in paediatrics.

Ibuprofen is prescribed for children for the treatment of acute pain and fever, and for juvenile idiopathic arthritis. The pharmacokinetic characteristics of ibuprofen in children are similar to those in adults and the relationship between dose and response is linear over the range 5-10 mg/kg. Clinical trials of ibuprofen have shown the effective dose range to be 7.5-10 mg/kg. The maximum reduction in temperature occurs 3-4 hours after administration. In comparative clinical trials, ibuprofen has been shown to be equally as effective as or more effective than paracetamol as an analgesic and antipyretic and to have a longer duration of action; it is also as effective as aspirin. The adverse effects of ibuprofen are similar to those of other non-steroidal anti-inflammatory drugs but clinical experience suggests that ibuprofen is better tolerated by children than adults and it is safer in overdose than paracetamol and aspirin.

Acute Disease↗
PubMed2002

Frequency of adverse drug reactions in children: a prospective study.

AIMS: To assess the frequency of adverse drug reactions (ADRs) in children in France. METHODS: In a prospective study over a period of 1 week, we evaluated the incidence of ADRs (1) as a cause of admission to a regional children's hospital; (2) occurring during hospitalization in a regional children's hospital; and (3) as a cause of consultation with private paediatricians. RESULTS: Four out of 260 children were admitted to the regional children's hospital for ADRs (1.53% [0.42, 3.89]) and six developed ADRs during hospitalization (2.64% [0.97, 5.66]), 4/428 attended the Accident and Emergency Department for ADRs (0.93% [0.25, 2.37]) and 8/1192 consulted a private paediatrician for ADRs (0.67% [0.29, 1.31]). CONCLUSIONS: Our results are in agreement with the incidence of ADRs in children found in others countries.

Child↗
PubMed2002

Amoxicillin/clavulanic acid is ineffective at preventing otitis media in children with presumed viral upper respiratory infection: a randomized, double-blind equivalence, placebo-controlled trial.

AIMS: To assess the equivalence of amoxicillin/clavulanic acid and placebo in the prevention of acute otitis media in children at high risk of acute otitis media who develop upper respiratory tract infection. METHODS: This was a multicentre, equivalence, randomized, double-blind trial of two parallel groups comparing 5 days of amoxicillin/clavulanic acid 75 mg kg-1 day-1 (i.e. 25 mg kg-1 every 8 h) and placebo. The main outcome measure was acute otitis media occurring within 8-12 days of initiating treatment. RESULTS: Two hundred and three infants, aged 3 months-3 years with upper respiratory tract infection over 36 h and a history of recurrent acute otitis media were included over 8.5 months. Two children were lost to follow-up. Patient characteristics were similar in both groups. In the intention to treat analysis the frequency of acute otitis media was 16.2% (16/99) in the placebo group and 9.6% (10/104) in the amoxicillin/clavulanic acid group (P = 0.288). The difference between acute otitis media rates was 6.6% (one-sided 95% confidence interval of 14.3%). The occurrence of side-effects was similar in the amoxicillin/clavulanic acid and placebo groups. CONCLUSIONS: The difference in effectiveness between antibiotic and placebo was not greater than 14.3%, and we calculated that 94 children would need to be exposed to antibiotics to avoid six cases of acute otitis media. In view of the risk of development of resistance due to frequent exposure to antibiotics, our study supports the need for reduction in the administration of antibiotics in upper respiratory tract infection even in children at high risk of acute otitis media.

Acute Disease↗
PubMedDate not supplied

[Chemical submission: a literature review].

The aim of this review is to describe the present knowledge about chemical submission. The number of scientific publications on this phenomenon has increased over the last 10 years. Perpetrators choose drugs which act rapidly, produce desinhibition, sedation, and anterograde amnesia during the abuse. Ethanol and benzodiazepines are the most frequently used. A few drugs, including flunitrazepam and gamma-hydroxybutyric acid (GHB), have received widespread media coverage. Toxicological investigations on blood, urine or hair samples allow to detect the substance used. Every effort should be made to collect appropriate specimens as quickly as possible. Gas chromatography-mass spectrometry is at present the most appropriate analytical method to detect these drugs in a biological specimen.

Dominance-Subordination↗