Pharmacokinetics and absolute bioavailability of phenobarbital in neonates and young infants, a population pharmacokinetic modelling approach.

Phenobarbital is widely used for treatment of neonatal seizures. Its optimal use in neonates and young infants requires information regarding pharmacokinetics. The objective of this study is to characterize the absolute bioavailability of phenobarbital in neonates and young infants, a pharmacokinetic parameter which has not yet been investigated.

Population pharmacokinetics of ertapenem in juvenile and old rats.

Ertapenem is a parenteral broad-spectrum carbapenem active against Gram-negative pathogens, which has been approved for treatment of different infectious situations in adults and children. Favourable pharmacokinetics and pharmacodynamics have been established in young adults. In the elderly, dosing regimen adaptations are not recommended.

Population pharmacokinetic analysis during the first 2 years of life: an overview.

Three decades after its introduction, pharmacokinetic population approaches have become a reference method for drug modelling, particularly in paediatrics. The main practical limitation in this specific population is the collected blood volume. Pharmacokinetic population approaches using sparse sampling may resolve this issue.

Vancomycin: Predictive Performance of a Population Pharmacokinetic Model and Optimal Dose in Neonates and Young Infants.

Introduction: Model evaluation is an important issue in population pharmacokinetic analyses. The objectives were to evaluate the predictive performance of previously published pediatric population pharmacokinetic models for vancomycin in a new data set and to propose an optimal dose to obtain a vancomycin concentration target.

Methods: External evaluation was conducted for all the published models of vancomycin in neonates and young infants with a new data set of 70 patients.

Vancomycin: a review of population pharmacokinetic analyses.

Despite nearly five decades of clinical use, vancomycin has retained a significant and uncontested niche in the antibacterial arsenal because of its consistent activity against almost all Gram-positive bacteria. Nevertheless, major vancomycin toxicities have been reported in the literature - in particular, nephrotoxicity and ototoxicity. Vancomycin pharmacokinetics have been described in numerous studies for 25 years.

[Manufacturing waste of hemodialyzers decreases oxidative phosphorylation of mitochondria isolated from rats].

Introduction: The persistence of manufacturing waste in hemodialysers is a neglected aspect of lack of hemodialysis biocompatibility. The effect of waste was tested on mitochondria isolated from rat liver.

Material And Methods: After throwing the first two liters of the rinse solution of hemodialysers, the third liter is lyophilized.

Effects of L-Dopa on circadian rhythms of 6-OHDA striatal lesioned rats: a radiotelemetric study.

Temporal variation in the motor function of Parkinson's disease (PD) patients suggests the potential importance of a chronobiological and chronopharmacological approach in its clinical management. We previously documented the effects of striatal injection of 6-OHDA (as an animal model of PD) on the circadian rhythms of temperature (T), heart rate (HR), and locomotor activity (A). The present work assessed the possible influence of L-Dopa on these same rhythms in the 6-OHDA animal model of PD.

Effects of induced hyperthermia on pharmacokinetics of ropivacaine in rats.

Ropivacaine is a local anaesthetic used for epidural anaesthesia and postoperative pain relief. Hyperthermia is a very common sign of infection associated with variations in physiological parameters, which may influence drugs pharmacokinetics. The aim of this study was to determine the effects of induced hyperthermia on ropivacaine pharmacokinetics in rats.

[Aspirin in decompression sickness].

Objective: We have performed a survey on the use of aspirin in decompression sickness (DCS) treatment in French hyperbaric centers'. We also conducted a review of literature to determine if aspirin was beneficial to treat human victims of DCS.

Methods: Prospective observational study investigating French hyperbaric centers' prescription of aspirin to DCS' divers victims.

Effects of hyperthermia on pharmacokinetics of ertapenem in rats.

The aim of this study was to document the influence of hyperthermia on the pharmacokinetics of ertapenem. Two groups of Wistar rats, normothermic (n = 6) and hyperthermic (n = 8), were injected a single intravenous bolus of ertapenem (15 mg/kg of body weight). Hyperthermia-induced animals were placed in a water-bath at 47 degrees C and control group animals were kept in a water-bath at 25 degrees C to obtain a stable mean core temperature of 39.

Clinical chronopharmacology in the elderly.

The behavior and effects of medications may be modified in the elderly. Factors contributing to such alterations may involve differences in drug pharmacokinetics and response and/or social and economic factors that affect nutrition and compliance to medications. Many studies have been devoted to such factors, but most of them have not taken into account chronopharmacologic data.

Independent-model diagnostics for a priori identification and interpretation of outliers from a full pharmacokinetic database: correspondence analysis, Mahalanobis distance and Andrews curves.

Population pharmacokinetic (PK) (or pharmacodynamic (PD)) modelling aims to analyse the variability of drug kinetics (or dynamics) between numerous subjects belonging to a population. Such variability includes inter- and intra-individual sources leading to important differences between the variation ranges, the relative concentrations and the global shapes of PK profiles. These various sources of variability suggest that the distance metrics between the subjects can be examined under different aspects.

Rhythmic pattern in pain and their chronotherapy.

Pain control is one of the most important therapeutic priorities; nonetheless, inadequate pain relief remains a significant health care issue. Thus, it is important to determine whether the analgesic effect can be improved by using the chronopharmacological approach. This paper reviews the data on the rhythmic patterns in pain level and their chronotherapy.

Biological rhythms: a neglected factor of variability in pharmacokinetic studies.

Biological rhythms may influence drug response (chronopharmacology) and some chronopharmacological studies have underlined the influence of time of day on drug pharmacodynamics and pharmacokinetics. The aim of the present review is to underline how biological rhythms may interfere with drug kinetics and to try to underline when, how, and why taking into account the moment of administration of a drug. Many physiological factors, possibly implicated in different steps of the fate of drugs in the organism (e.

Effects of a seven-day continuous infusion of ropivacaine on circadian rhythms in the rat.

The present study was conducted to evaluate the effect of a 7 d continuous infusion of ropivacaine on the 24 h rhythms of body temperature, heart rate, and locomotor activity. After an initial 7 d baseline, rats were randomly divided into two groups of 4 rats each to receive ropivacaine or saline via an osmotic pump for 7 consecutive days. The pumps were removed thereafter and observed during a 7 d recovery span.

Population pharmacokinetics of ceftriaxone and pharmacodynamic considerations in haemodialysed patients.

Objectives: To determine the pharmacokinetic parameters of ceftriaxone following an infusion in haemodialysed outpatients and to use these parameters for an optimisation of dosing based on pharmacodynamic indices.

Methods: Fifty haemodialysed patients were enrolled in a single-centre, prospective, open-label study. They received short intravenous infusions of ceftriaxone 1 or 2 g every 48 hours for bronchopneumonia immediately after the dialysis session.

Cluster analysis: an alternative method for covariate selection in population pharmacokinetic modeling.

To be analyzed, the heterogeneity characterizing biological data calls for using appropriate models involving numerous variables. A high variable number could become problematic when one needs to determine a priori the most significant variable combination in order to reduce the inter-individual variability (IIV). Alternatively to multiple introductions of single variables, we propose a single introduction of a multivariate variable.

[Involvement of a public pharmacology laboratory in pharmacokinetic studies].

Pharmacokinetic studies can be performed before or after a drug is marketed. Indeed, extensive use of a new drug can uncover situations that it has not been possible to investigate before market application. Hospital departments of pharmacology are often involved in these complementary studies.

The effects of a normal protein diet on levodopa plasma kinetics in advanced Parkinson's disease.

LevoDOPA given orally may compete with the neutral aminoacids contained in food for its absorption in the small intestine. LevoDOPA plasma kinetics of the morning intake with 'french' breakfast (low protein content) were compared with those of the noon intake with lunch (normal protein content) in 20 advanced parkinsonian patients (mean disease duration: 10 years). The galenic form and the dosage of levoDOPA were strictly the same for morning and noon intakes in each patient.

Method for simultaneous measurement of norepinephrine, 3-methoxy-4-hydroxyphenylglycol and 3,4-dihydroxyphenylglycol by liquid chromatography with electrochemical detection: application in rat cerebral cortex and plasma after lithium chloride treatment.

An assay was developed to quantify norepinephrine (NE) and its metabolites (MHPG and DHPG) by high-performance liquid chromatography with electrochemical detection method (HPLC-ECD) in brain tissue and plasma of rats treated by LiCl. Separation on C(18) column was obtained by a mobile phase consisting of 4.5% methanol in buffer (0.

Moxifloxacin penetration in bronchial secretions of mechanically ventilated patients with pneumonia.

The pharmacokinetics of moxifloxacin was studied in 17 mechanically ventilated patients with pneumonia. Patients were given 400 mg of moxifloxacin intravenously. Blood samples and bronchial secretions were taken on days 1 and 4.

Population pharmacokinetics of moxifloxacin in plasma and bronchial secretions in patients with severe bronchopneumonia.

Objective: Our objective was to construct a population pharmacokinetic model for moxifloxacin disposition in plasma and bronchial secretions in patients with severe bronchopneumonia who were mechanically ventilated.

Methods: Seventeen patients receiving 400 mg moxifloxacin intravenously daily were enrolled in this multicenter, prospective, open-label study. Blood and bronchial samples were collected on days 1 and 4.

Circadian rhythms of oxidative phosphorylation: effects of rotenone and melatonin on isolated rat brain mitochondria.

Mitochondrial experiments are of increasing interest in different fields of research. Inhibition of mitochondrian activities seems to play a role in Parkinson's disease and in this regard several animal models have used inhibitors of mitochondrial respiration such as rotenone or MPTP. Most of these experiments were done during the daytime.

Tacrolimus and sirolimus decrease oxidative phosphorylation of isolated rat kidney mitochondria.

1. Tacrolimus and sirolimus are potent immunosuppressors used in transplantation. Tacrolimus has been suspected to alter mitochondrial respiration of different tissues but sirolimus has not been evaluated.