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Biomedical subjects

G Olive

Publications and source records attributed to G Olive.

At least 37 records · Page 2Linked to original sources
PubMed1996

Effect of stiripentol on carbamazepine plasma concentration and metabolism in epileptic children.

OBJECTIVE: To study the relationship between the plasma concentration of stiripentol (STP), a new antiepileptic drug, and its inhibitory effect on the formation of carbamazepine epoxide (CBZE) in epileptic children treated with carbamazepine (CBZ) either alone or in combination with another antiepileptic drug. METHODS: Minimum plasma concentration of antiepileptic drugs was measured before initiation of STP therapy (day 0) and on days 28 (STP 60 mg.kg-1.day-1) and 84 (STP 90 mg.kg-1.day-1) by HPLC. RESULTS: The CBZE/CBZ plasma concentration ratio decreased exponentially with increasing minimum plasma STP concentration (r = 0.80). The asymptote of the curve allowed the calculation of the minimum plasma STP concentration required to obtain the maximum inhibitory effect, i.e. 6.7 mg.l-1. CONCLUSION: The inhibitory effect of STP on CBZ metabolism expressed as the CBZE/CBZ plasma concentration ratio is dependent on STP plasma concentration, with a maximum effect at an average of 7 mg.l-1. The present data suggest that in order to evaluate the anticonvulsant efficacy of STP as add-on therapy, the minimum plasma STP concentration should be maintained above 7 mg.l-1 and the dosage of CBZ should simultaneously be decreased in steps by more than 50% to minimize the change in CBZ plasma concentration.

Adolescent↗
PubMed1996

Non invasive in vivo study of the maturation of CYP IIIA in neonates and infants.

OBJECTIVE: Cytochrome P450 III (CYP III) has previously been demonstrated in vitro in fetal liver. METHODS: A study was performed in 7 premature, 13 term neonates and 30 infants to assess whether or not maturation had any influence on CYP IIIA activity in children from birth to 1 year of age. A simple non invasive procedure was used (6 beta OHF/FF concentration ratio in a morning spot urine sample). RESULTS: The 6 beta OHF/FF ratio was 7.2, 7.9 and 5.0 in premature and term neonates and infants, respectively. CYP IIIA activity is present at birth, with a 6 beta OHF/FF ratio comparable to adults. Its activity seemed lower in infants. This might be due to the decrease in CYP IIIA7 activity during maturation after birth, which might be more rapid than the increase in CYP IIIA3/4 activity.

Age Factors↗
PubMed1996

Culture of endothelial cells from human placental microvessels.

Endothelial cells are known to participate in angiogenesis, adaptation of vascular tonus and maintenance of blood fluidity in the microcirculation. To investigate these functions in the placenta, we devised a method of isolation and culture of endothelial cells from villous microvessels. In primary culture, these intraplacental endothelial cells exhibited many features observed in microvascular endothelium from other organs: spindle-shape, rosette associations, circular arrangements and confluence. In contrast to the confluent endothelial cells derived from the umbilical vein, cells from microvessels did not form a cobblestone network. After trypsin digestion of microvessels, magnetic microbeads coated with S-Endol immunoglobulin, antithrombomodulin and Ulex europaeus-I lectins were tested for sorting endothelial cells. Only the microbeads coated with antithrombomodulin allowed a suitable magnetic cell separation after trypsinization. By contrast, the microbeads coated with each of these antibodies or with lectins attached to confluent cells from the second passage. The microbeads detached from the cells at different rates. Their examination by scanning microscopy indicates that a portion of these microbeads was phagocytosed. Microvascular endothelial cells from the second passage were intensively stained by the anti-von Willebrand reaction and only weakly by the anti-smooth muscle alpha-actin reaction. They incorporated acetylated-low density lipoproteins coupled to a fluorescent probe. The positive reactions against the anti-von Willebrand factor and the uptake of the fluorescent acetylated-low density lipoproteins were modified after eight passages.

Absorption↗
PubMed1996

Pharmacokinetics of the individual enantiomers of vigabatrin in neonates with uncontrolled seizures.

The antiepileptic drug vigabatrin (VGB) is a selective irreversible inhibitor of GABA-transaminase. It is administered as a racemic R(-), S(+) mixture, but the pharmacological activity of vigabatrin resides in the S(+) enantiomer and the R(-) enantiomer is inactive. The pharmacokinetic parameters of the two enantiomers have been studied after administration of a single oral 125 mg dose of the racemate to six neonates. The mean values of Cmax and AUC of the S(+) enantiomer were significantly lower (Cmax: 14.0 +/- 4.3 mg l-1; AUC: 143 +/- 44 mg l-1 h) than those of the R(-) enantiomer (Cmax: 34.1 +/- 9.5 mg l-1; AUC: 231 +/- 88 mg l-1 h), whereas no significant difference in the time to reach Cmax (S(+): 2.1 +/- 1.1 h; R(-): 2.2 +/- 1 h) was observed between the two enantiomers. During chronic administration (125 mg twice daily over 4 days), there was no evidence of accumulation of either enantiomer.

Anticonvulsants↗
PubMed1996

Influence of concurrent antiepileptic medication on the pharmacokinetics of lamotrigine as add-on therapy in epileptic children.

1. Lamotrigine is a new antiepileptic drug, chemically unrelated to currently used antiepileptic medication. Its pharmacokinetics can be influenced by concomitant antiepileptic medication. 2. This study was performed to assess the pharmacokinetic profile of lamotrigine in three groups of children treated with different types of comedication: drugs known to induce, to inhibit or to have no clinically significant influence on drug metabolism, respectively. 3. Thirty-one children aged 6 months to 5 years were included and received a 2 mg kg-1 single oral dose. Lamotrigine plasma profiles were different between the three comedication groups. The half-lives (mean +/- s.d.) were: 7.7 +/- 1.8 h, 21.9 +/- 6.8 h, 44.7 +/- 10.2 h in the "inducer', "other' and "inhibitor' groups respectively. 4. Patients were then dosed to steady state, with the dosage adjusted on the basis of the single dose pharmacokinetics to achieve a minimum plasma concentration between 1.5 and 3 mg l-1. The mean minimum plasma concentration for the three groups was 2.54 +/- 1.28 mg l-1 at steady state. 5. Dosage of lamotrigine can be optimised with knowledge of the metabolic effects of antiepileptic comedication.

Anticonvulsants↗
PubMed1996

Antipyretic efficacy of tiaprofenic acid in febrile children.

In children, tiaprofenic acid (TA), a non steroidal antiinflammatory drug, propionic-acid derivative, has been proven effective in the treatment of symptoms of tonsillitis and pharyngitis but not yet in the symptomatic treatment of fever. This double-blind, parallel group, placebo (Pl) controlled study was designed in order to demonstrate the antipyretic activity of TA. The co-prescription of other antipyretic medications in children may therefore be avoided. Two groups of children, 29 (TA group) and 26 (Pl group), were included and received either 4.2 +/- 0.5 mg/kg of TA given orally in a single dose or a Pl match. Rectal temperature was recorded just before and 1, 2, 4 and 6 hours after dosing. The maximum temperature decrease was significantly greater in the TA group (-1.3 degrees C +/- 0.7 degree C) than in the Pl group (-0.4 degree C +/- 0.8 degree C). The percentage of children who needed a rescue treatment during the study was 35% (10/29) and 62% (16/26) in the TA and Pl group, respectively. The rescue treatment was composed of a single oral acetaminophen dose in case of fever above 39.5 degrees C or if the temperature decrease was not at least equal to 0.6 degree C four hours after dosing. No major side effect was reported by the parents during the study period. In conclusion, TA at a single mean 4.2 mg/kg oral dose, is an effective antipyretic drug in febrile children. The duration of the antipyretic effect was estimated as at least four hours.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed1996

A randomized, double-blind, multicentre controlled trial of ibuprofen versus acetaminophen and placebo for symptoms of acute otitis media in children.

Two hundred and nineteen children (boys: 56%, girls: 44%) were included in a randomized, double-blind, multicentre (4 centres) controlled trial designed to assess the efficacy and safety of ibuprofen (IBU) in the treatment of 1 to 6 year-old children with otoscopically proven acute otitis media (AOM), either unilateral or bilateral. They randomly received 10 mg/kg IBU (n = 71), or acetaminophen (PARA) (n = 73) or placebo (PLA) (n = 75), orally, tid, for 48 hours. All received oral cefaclor (Alfatil, Lilly, France) for seven days. They were evaluated before (D0) and at the end of treatment (D2). The main criterion of response was the aspect (landmarks and color) of the tympanic membrane assessed on a semi-quantitative scale from 0 to 6. Other criteria, assessed on semi-quantitative scales, included relief of pain (0 or 1), rectal temperature (0 to 2), and overall evaluation by parents of the improvement of quality of life on three items: appetite (0 to 2), sleep (0 to 2), and playing activity (0 to 2). The results at D2 were as follows: there was no significant difference between treatment groups as to the main criterion, but only a trend for IBU and PARA to do better than PLA but not for IBU to do better than PARA. From these data there is no argument to emphasize the utility of non-steroidal anti-inflammatory drugs (NSAIDs) in treating the inflammatory signs of the tympanic membrane in otitis. There was a statistically significant difference between treatment groups at D2 for pain, IBU being superior to PLA (P < 0.01): 7%, 10% and 25% of the children were still suffering at D2 in the IBU, PARA and PLA treatment groups, respectively. The difference between PARA and PLA for pain was not statistically significant. There was no significant difference between treatment groups for the other criteria. All treatments were well and equally tolerated. Although no significant difference was found between the treatment groups on the aspect of the tympanic membrane, the efficacy of IBU was evidenced on the relief of pain, the symptom that most disturbs the child.

Acetaminophen↗
PubMed1996

Dialysis clearance of buflomedil in hemodialysed patients.

Buflomedil (CAS 55837-25-7, Fonzylane) is a peripherally vasoactive drug which improves nutritional blood flow in ischaemic tissue of patients with peripheral vascular disease by the way of an increase of perfusion in the microcirculation. Ten hemodialysed patients with chronic renal failure treated with intravenous infusion of 400 mg of buflomedil during 4 h of dialysis were included in the first study. This study was carried out to determine the dialysis plasma clearance and the amount of drug dialysed during the first intravenous administration of buflomedil. The dialysis clearance calculated from the amount recovered in dialysate was (mean +/- SD) 25.4 +/- 25.6 ml/min. The drug recovery resulting from hemodialysis represented a small fraction of the dose (< or = 5%). A second study was carried out to determine the accumulation of buflomedil in chronic hemodialysed patient. The drug concentration were measured before and at the end (4 h) of the infusion of buflomedil in six other patients maintained on intermittent hemodialysis (3 per week) for 4 weeks. The average Cmin and Cmax were stable during the 12 successive dialyses (mean +/- SD intervals were between 0.36 +/- 0.53 and 0.66 +/- 0.79 microgram/ml for Cmin and between 5.15 +/- 2.19 and 7.37 +/- 1.76 micrograms/ml for Cmax), showing no trend of accumulation of buflomedil. These results agree with the pharmacokinetics of the drug which is mainly metabolised in the liver and has a low renal clearance. Dialysis is unable to modify significantly the plasma concentration of the drug in regularly dialysed patients.

Aged↗
PubMed1996

Pharmacokinetics of tiaprofenic acid in infants after a single oral dose.

Ten healthy infants (15.2 +/- 10.6 months old, range 6-35) anesthetized for minor surgery were given a single oral dose (3 mg x kg-1) of tiaprofenic acid (TA). Seven venous blood samples and 0-12 h urine were collected. TA concentrations in plasma and urine were measured by HPLC. Within the whole group the mean +/- SD kinetic parameters were: Cmax: 10.55 +/- 3.31 mg x l-1, Tmax: 1.73 +/- 0.87 h, AUC0-1 32.53 +/- 4.42 mg x l-1 x h, AUC0-infinity 35.33 +/- 4.73 mg x l-1 x h, t1/2 1.82 +/- 0.48 h, Cl/F: 0.09 +/- 0.01 l x h-1 x kg-1, VZ/F: 0.23 +/- 0.08 l x kg-1. Renal clearance was 0.030 +/- 0.009 l x h-1 x kg-1. 32% of the TA dose was recovered in urine, 60% of which was conjugated. AUC0-8h increased significantly with age. The TA kinetic parameters were close to those in 3 to 11-year-old children. The present study suggests slight differences in the TA kinetics between infants and adults. However, the lack of an evidenced direct relationship between plasma TA concentration and either efficacy or tolerance suggests that the TA dose regimen in infants may not have to be different from that in adults.

Administration, Oral↗
PubMed1995

Pharmacokinetics of cetirizine in 2- to 6-year-old children.

Eight children (3.84 +/- 1.17 years old) received a single oral 5 mg cetirizine dose (0.32 +/- 0.07 mg.kg-1) as a 10 mg.ml-1 solution, 1.73 (+/- 0.64) hours before a minor surgical intervention (mean duration +/- SD = 0.90 +/- 0.25 h). Seven venous blood samples were collected before administration (t0) and 0.5 h, 1.5 h, 4 h, 8 h, 12 h and 24 h after dosing, and urine samples were collected up to 24 hours after the dose. The mean +/- SD kinetic parameters were: peak plasma level (Cmax) 607 +/- 231 micrograms.l-1 reached in 1.93 +/- 1.39 h (tmax), elimination half-life (t1/2) 5.55 +/- 0.98 h, area under the plasma concentration time curve (AUC0-infinity) 4,772.1 +/- 1,318.4 micrograms.l-1.h, mean residence time (MRT) 8.13 +/- 1.31 h, apparent plasma clearance (Cl/f) 1.27 +/- 0.80 ml.min-1.kg-1, apparent volume of distribution (Vz/f) 0.60 +/- 0.38 l.kg-1. Urinary recovery was 38.4 +/- 9.9% (n = 4) of the dose. Renal clearance was 0.42 +/- 0.10 ml.min-1.kg-1 (n = 6). No influence of age on the cetirizine parameters was evidenced among this group, except for MRT (p < 0.05) which decreases with age. When compared with results in adults, elimination half-life (t1/2) was twice as short and apparent clearance twice as great. These results suggest that a higher dosage b.i.d. may be required in children.

Administration, Oral↗
PubMed1995

Mixed culture of pericytes and endothelial cells from fetal microvessels of the human placenta.

To explore the role of perivascular cells in angiogenesis and vasomotricity, placental cultures of perivascular cells were performed from calibrated villi excised from term placentas. Microvessels were isolated using repeated digestion of villi by collagenase-dispase and purification by Percoll gradients. Plated on Petri dishes, the microvessels became adherent to the gelatin matrix permitting to cells to proliferate. Cells were harvested and subcultured. Endothelial and pericyte cell lines were identified by phase contrast microscopy. Pericyte number predominated rapidly, the endothelial cells remaining visible. After seven days, cells started to cluster, thus piled up and built numerous nodules. Medium-size oval endothelial cells were stained by anti-von Willebrand factor and anti-IgG coupled to fluorescein. Large cells with irregular border reacted to smooth muscle anti-alpha-actin and anti-IgG coupled to fluorescein. There was no cross-reaction of these two cell types with the antibodies. In contrast, nodules were stained by both immunostainings. Endothelial cells reacting to von Willebrand factor antibody were frequently associated to the nodule. The isolation of microvessels from the human placenta described in this study allowed the establishment of cultures of endothelial cells and pericytes that show: i) rapid predominance of pericytes over endothelial cells, ii) formation of nodules, iii) participation of endothelial cells and pericytes to nodules formation.

Actins↗
PubMed1994

Safety, tolerability, efficacy and plasma concentrations of tropisetron after administration at five dose levels to children receiving cancer chemotherapy.

In a double-blind, placebo-controlled, escalating dose study, 44 children receiving cancer chemotherapy of various degrees of emetogenicity were randomly allocated to once-daily treatment with tropisetron 0.05 mg/kg (6 patients), 0.10 mg/kg (5 patients), 0.20 mg/kg (6 patients), 0.33 mg/kg (6 patients), 0.50 mg/kg (6 patients) or placebo (15 patients). All doses of tropisetron were well tolerated; no tropisetron recipient discontinued treatment because of intolerance and no adverse effect could be plausibly correlated to tropisetron administration. Therapeutic plasma concentrations of tropisetron (> 3 ng/ml) were present for 9 h after administration of doses of 0.10 mg/kg or more. Tropisetron at doses of at least 0.20 mg/kg was significantly more effective in preventing vomiting than lower tropisetron doses or placebo, both in terms of treatment failure (> four vomits) (P = 0.015) and patient and investigator efficacy ratings (P = 0.04 for investigator rating; P = 0.035 for patient rating). Further comparative studies of the efficacy of tropisetron in chemotherapy-induced emesis in children are warranted.

Adolescent↗
PubMed1994

Biotransformation of caffeine in human liver microsomes from foetuses, neonates, infants and adults.

1. Caffeine metabolism was studied in human liver microsomes from foetuses (n = 10), neonates (n = 10), infants (n = 9) and adults (n = 5). Caffeine and its metabolites, 1-3-7-trimethyluric acid, paraxanthine, theophylline and theobromine, were assayed by h.p.l.c. Methoxyresorufin-O-demethylase activity (MEROD) was determined and immunoquantifiable levels of CYP1A2 were measured. 2. The formation of the dimethylxanthines by N-3, N-7 or N-1-demethylation was significantly less in foetuses, neonates and infants than in adults, as shown previously in vivo. The formation of 1-3-7-trimethyluric acid (C-8-hydroxylation) was not significantly different between age groups. The production of total dimethylxanthines, paraxanthine and theophylline increased significantly with age within the neonate-infant group over at least the 0-300 day range (rs = 0.739, 0.667, 0.682, respectively). These data differ from those reported in vivo which suggested that N-3 and N-7-demethylations matured at about 120 days. The difference in maturational profiles of each metabolic pathway suggests that the reactions depend on different isoenzymes. The delay in the maturation of N-1 compared with N-3 and N-7-demethylation is in agreement with previous in vivo data. 3. In the neonate-infant group, only N-3-demethylation correlated with both MEROD activity (rs = 0.681; P < 0.05) and CYP1A2 microsomal concentration (rs = 0.454; P approximately 0.05), suggesting that, as in adults, this reaction depends on CYP1A2. 4. In the foetal samples, the production of total dimethylxanthines, paraxanthine and theobromine decreased significantly (rs = -0.879, -0.767, -0.708, respectively) with increasing gestational age.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

[Pharmacokinetics of diphemanil methylsulfate in infants].

BACKGROUND: Diphemanil methylsulfate is an atropin-like drug used in some infants suffering from vagal bradycardia. Its pharmacokinetic parameters are known for adults but not for infants. The report describes these parameters in six infants. POPULATION AND METHODS: Five infants aged 35 to 109 days (mean: 62 +/- 28) and weighing 3.5 to 5.3 kg (mean: 4.3) were included in the study with the formal consent of their parents. All suffered from vagal hyperreactivity. The sixth younger full-term infant was aged 10 days and weighed 4 kg. They were given a single dose (3 mg/kg) of diphemanil methylsulfate orally, after a minimal fast of 4 hours. Blood samples were collected at T0 and 3, 6, 8, 12 and 24 hours after administration. Urines were also collected from 1 hour before drug administration to 24 hours after. Plasma concentrations of diphemanil methylsulfate were measured by gas-exchange chromatography. RESULTS: The peak plasma concentration in the five infants occurred at 3.9 +/- 2.3 hours (range: 2.9-8 hours). Half-life was 8.6 +/- 2.4 hours and tended to decrease with age. All the other parameters were identical to those found in adults. The peak plasma concentration occurred in the sixth younger infant at 2.9 hours, with a half-life of 17.2 hours. Renal clearance was high (0.3 l/h/kg). CONCLUSION: The relatively long half-life of diphemanil methylsulfate allows this drug to be given every 8 hours. This longer interval is more comfortable for the patients and their parents. The high renal clearance suggests that this drug is excreted by both glomerular filtration and tubular secretion.

Age Factors↗
PubMed1993

Pharmacokinetics of diphemanil methylsulphate in infants.

The pharmacokinetics of diphemanil methylsulphate was evaluated after oral administration of a single 3 mg.kg-1 dose to 5 infants being treated for symptomatic bradycardia. The mean pharmacokinetic parameters of oral diphemanil methylsulphate in infants were similar to those in adults. The mean half-life was 8.6 h. This would allow administration three times a day in infants instead of four to six times a day, as currently prescribed. The mean residence time decreases significantly with age (Spearman's r' = -1), and there is a trend for the half-life to decrease with age (r' = -0.9; NS), suggesting an influence of maturation on its elimination.

Administration, Oral↗
PubMed1993

Effect of age and disease on the pharmacokinetics of nimesulide.

Nimesulide is a nonsteroidal anti-inflammatory agent with additional antipyretic and analgesic activity. The recommended dosage is 100 to 200 mg twice daily orally or rectally. The pharmacokinetics profile of nimesulide has been studied in patients with a predisposition for altered pharmacokinetics. The pharmacokinetic profile of nimesulide and its hydroxy metabolite was not altered when the drug was administered in a standard regimen (100mg twice daily) to elderly patients aged < 80 years, suggesting that dosage adjustment is not necessary for such patients. In children aged 7 to 9 years, nimesulide 50mg administered in a granular formulation showed a tendency for greater absorption and elimination than that recorded for adults administered nimesulide in tablet form. These results suggest that the pharmacokinetic profile of this paediatric formulation should be assessed in children aged < 7 years to determine whether their dosage should be adjusted. In patients with moderate renal insufficiency, the pharmacokinetic profile of nimesulide was not altered even though the terminal elimination half-life of its hydroxy metabolite was greater and this resulted in slight accumulation with multiple dose administration in a standard regimen. This slight effect was not considered to be clinically significant and therefore dosage adjustment for patients with moderate renal impairment appears unnecessary. Administration of nimesulide to patients with severe renal failure should be avoided until the propensity and significance of hydroxy-nimesulide accumulation is quantified in this patient group. The pharmacokinetic profile of nimesulide has not been determined in patients with hepatic disease.(ABSTRACT TRUNCATED AT 250 WORDS)

Age Factors↗