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Biomedical subjects

G Paintaud

Publications and source records attributed to G Paintaud.

At least 55 records · Page 3Linked to original sources
PubMed1993

Lack of effect of amoxycillin on the absorption of ofloxacin.

Amoxycillin and ofloxacin are both well absorbed after oral administration, despite being hydrophilic. We have studied the possibility of competition between these two drugs for a carrier-mediated transport system, since both drugs are absorbed by saturable processes in the rat small intestine. Oral doses of amoxycillin (3 g) and ofloxacin (400 mg) were given separately and in combination to six healthy volunteers. Blood samples were taken over 30 h and plasma concentrations of the respective drugs were measured by HPLC. Amoxycillin did not alter the pharmacokinetics of ofloxacin.

Adult↗
PubMed1993

The reproducibility of quinine bioavailability.

Plasma concentrations of quinine were measured in six healthy volunteers after a duplicate administration of 15 mg kg-1 of quinine hydrochloride orally and the administration of 15 mg kg-1 of quinine dihydrochloride as an infusion over 6 h. Quinine absorption rate devised by deconvolution was shown to be complete in less than 2 h. The mean (+/- s.d.) fraction available (F) was 0.76 (0.11) after both oral doses and maximum plasma drug concentrations occurred at 1.90 (0.83) h and 2.00 (0.30) h, respectively. The reproducibility of absorption was high, with a within-subject coefficient of variation of less than 10% for Cmax, AUC and F. Thus, quinine absorption is extensive, fast and reproducible in healthy volunteers.

Administration, Oral↗
PubMed1992

Dose-dependent absorption of amoxicillin in patients with an ileostomy.

Amoxicillin was given as single doses of 375, 700, 1500, 3000 and 6000 mg an oral suspension to four volunteers with an ileostomy and with no active intestinal disease after an overnight fast. The excretion of amoxicillin and its penicilloic acid was followed in samples taken from the ileostomy and in urine produced over 6 h. Beta-lactamase activity was measured in ileal fluid and none was found. The percentage of the dose recovered from the ileostomy increased successively from 8% at the lowest dose to 77% at the highest dose. A complementary excretion pattern of amoxicillin was found in the urine, amounting to 70% recovery at the lowest dose to 23% at the highest dose. The results confirm the dose-dependence of the absorption of amoxicillin, which could at least in part be due to specialised absorption of this drug in humans.

Adult↗
PubMed1992

Nonlinearity of amoxicillin absorption kinetics in human.

Specialised gastrointestinal absorption of amoxicillin has been suggested in man and has been demonstrated in animals. In order to study the rate and extent of amoxicillin absorption, six healthy subjects were given 500 mg IV and two oral doses (500 mg and 3 g as a suspension). Absorption kinetics was analysed by compartmental modelling, noncompartmental methods and by calculation of absorption rates using deconvolution. Dose-dependency of the extent of amoxicillin absorption was observed, with a lower than expected mean maximum plasma concentration (49%), and fraction of the dose absorbed (39%) after the 3 g dose calculated from the 500 mg dose, assuming kinetic linearity. Zero-order kinetics of absorption was apparent in some subjects after the 500 mg dose, both from model fitting and absorption rate profile. However, no pattern consistent with pure first-order or zero-order absorption was observed after both oral doses in any individual. The dose-dependency of amoxicillin absorption was confirmed by a trend to an increased time of absorption for the high dose. The results show the variable nature and nonlinearity of the gastrointestinal absorption of amoxicillin and indicate the involvement of a number of factors, in addition to simple diffusion.

Amoxicillin↗
PubMed1992

Discrepancy between bioavailability as estimated from urinary recovery of frusemide and total diuretic effect.

1. Frusemide was given at a dose of 60 mg as two oral controlled release (CR) formulations and as plain tablets in a randomised, balanced, three way cross over design to 26 healthy volunteers. Urinary volume, and contents of frusemide, sodium, chloride and potassium were measured in samples taken over 24 h. 2. There was a marked difference between the CR formulations on one hand and the plain tablets on the other, in excretion of frusemide and diuresis vs time. The total diuretic/saluretic effect was only marginally lower (19 and 28% respectively, P less than 0.05) after CR compared with plain tablets although the fraction absorbed was markedly decreased (39 and 51% lower, respectively, P less than 0.05), estimated as urinary recovery of frusemide. The total diuresis of the two CR formulations did not differ although the urinary recovery was significantly different (P less than 0.05). 3. The diuretic effect vs frusemide excretion rate showed minimal counter-clockwise hysteresis after plain tablets while the CR formulations produced clockwise hysteresis indicating tolerance. 4. In agreement with the concept of efficiency, the higher diuretic/saluretic effect per amount of excreted frusemide may be a consequence of the slower output of frusemide in urine with the CR formulations compared with plain tablets. The major part of the pharmacological effect was produced with a higher efficiency after CR compared with plain tablets. It should be noted that the pharmacokinetics of a drug and its pharmacodynamic potency independently determine the total response.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗
PubMed1991

Orthotopic liver transplantation for incurable alveolar echinococcosis of the liver: report of 17 cases.

Between 1986 and 1989, orthotopic liver transplantations were performed in our unit for 17 patients with incurable alveolar echinococcosis. Ten patients had hilar involvement (group I), and seven patients had posterior localization (five of them had chronic Budd-Chiari syndrome) (group II). The delay between diagnosis and the orthotopic liver transplantation was more than 48 mo in group Ia (six patients), less than 24 mo in group Ib (four patients) and less than 48 mo in group II. Previous operations were more common in group Ia than in group Ib and II. Five patients have died-four in group I and one in group II. The actuarial survival rate at 15 mo was 75%. Early reoperations were frequent (69%), mainly caused by rebleeding. Bacterial and fungal infections occurred only in group Ia (four cases) and group II (three cases). In eight patients (palliative group), residual foci of infected nonhepatic tissue occurred after surgery. The titer of specific antibodies decreased during the first 3 mo in all the patients but one. In patients with radical liver transplantation, the complete disappearance of specific antibodies occurred within 2 yr in four cases. In the remaining five patients, specific antibodies remained detectable, but no evidence of recurrence has been obtained up to now. In the palliative group, a peak of specific IgM occurred at 3 mo; an increase of specific IgG was observed later. The growth of residual parasitic foci was relatively slow, and all these patients remained asymptomatic with a mean follow-up of 19 mo. We conclude that orthotopic liver transplantation is feasible in incurable alveolar echinococcosis and could be proposed without delay to patients with parasitic Budd-Chiari syndrome or complicated secondary biliary cirrhosis. In the other cases, the best time to perform an orthotopic liver transplantation is more difficult to determine. Nevertheless, in the perspective of an orthotopic liver transplantation, the management of these patients has to change, and repetitive laparotomies for palliative surgical procedures have to be replaced by interventional radiology.

Adult↗
PubMed1990

[Complications in 52 liver transplantations excluding graft rejection].

We analyzed the postoperative complications excluding graft rejection in 52 consecutive orthotopic liver transplantations performed from March 1986 to November 1988 in 48 patients. Thirteen patients died: one intraoperatively, seven during the first 2 months, and five between 5 and 28 months. Complications were predominant during the first 3 months; infection was the most common complication. The main cause was viral agents. Cytomegalovirus was responsible for infection in 62 percent of cases, but was symptomatic in only 37 percent of patients and always had a favorable outcome. Six cases of disseminated candidiasis were observed with fatal outcome in 3 cases. Ten patients had septicemia due to Gram positive germs with a favorable course in all cases. Two patients required retransplantation on the 2nd postoperative day because of primary graft failure. Three patients had hepatic infarction which was fatal in one case. Technical complications were represented by intra-abdominal bleeding in 3 cases, perihepatic hematoma in 10 cases and stenosis of the biliary anastomosis in 8 cases; in one patient, partial portal vein thrombosis occurred; no hepatic arterial thrombosis occurred during the first postoperative days but this complication was diagnosed later in 3 instances by arteriography. Five out of 7 patients transplanted for malignant liver disease experienced recurrence which cause death in 4 cases. In 3 out of the 5 patients transplanted for postviral B cirrhosis, chronic active hepatitis occurred 6 months after transplantation and one of these patients had to be retransplanted at 13 months for recurrence of cirrhosis.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMedDate not supplied

Caffeine metabolism differences in acute hepatitis of viral and drug origin.

The 24-h urinary excretion rate of caffeine metabolites following 200 mg caffeine intake has been proved to be a valuable safe quantitative test of liver function. The pathological mechanism of acute hepatitis of viral and drug origin is different. In both diseases, the patient's caffeine metabolic capacity during the acute and the recovery period was compared. In the acute period, in both diseases, the strongly reduced metabolism of caffeine paralleled the variations of the usual biochemical tests. During the recovery period, in viral hepatitis, caffeine metabolism and biochemical tests returned to the normal values. In drug-induced hepatitis during the recovery period, caffeine metabolism remained severely impaired at a time when biochemical tests were back to the control levels. This discrepancy might be due to the histological or molecular toxic effects of the drug(s), irrespective of cytolysis. After drug-induced hepatitis, a caffeine test might be used to check the total recovery or to choose an adapted dosage of medicines.

Acute Disease↗
PubMedDate not supplied

[Issues in therapeutic drug monitoring evaluation].

A reassessment of the interest of therapeutic drug monitoring (TDM) is needed for a better definition of its applications. It rests on the hypothesis of the existence of an interindividual variability of the dose-effect relationship, this variability being influenced by pharmacokinetic variability. Different types of endpoints were used in validation studies (pharmacokinetic, indirect, economic) and few studies have used clinical endpoints. The question should be: does TDM allow for a better dose adjustment than one based only on criteria other than drug concentration? Retrospective studies have a 'diagnostic test' approach and only prospective clinical trials will provide a real validation. Factors which limit the setting up of such studies are: the number of subjects to include, the often imprecise measurement of drug exposure and poor knowledge of the pharmacokinetic-pharmacodynamic relationship and its variability.

Dose-Response Relationship, Drug↗
PubMedDate not supplied

Ciprofloxacin pharmacokinetics in young cystic fibrosis patients after repeated oral doses.

Until recently, only compassionate use of ciprofloxacin in children with cystic fibrosis was possible despite limited pharmacokinetic data. We studied five subjects with cystic fibrosis and exacerbation of pulmonary infection. A 15 mg/kg b.i.d. regimen of oral ciprofloxacin was administered. On the 15th day, eight blood samples were collected and plasma concentrations were measured by HPLC. The actual dose administered ranged from 10 to 14 mg/kg b.i.d., due to the fixed-dosage formulation. Corresponding AUC0-12 ranged from 8.2 to 11.9 mg.h/L. Plasma concentrations were maintained above individual MICs for a median time of 12.7 h over 24 h. The median area under the inhibitory curve was 52.8, which is about half the proposed target value for ciprofloxacin in pulmonary infections with Gram-negative bacteria such as Pseudomonas aeruginosa. A higher dose, administered from a specific formulation to ensure precise dosing, must be given in order to obtain adequate concentrations in cystic fibrosis children.

Administration, Oral↗
PubMedDate not supplied

[Pharmacokinetic studies in neonatology: regulatory and methodologic problems].

Pharmacokinetic studies in neonates are essential because of maturational changes in physiological functions during this period. International harmonization conferences have established guidelines for such studies, including recommendations on age ranges to be studied and description of methods and study design. Multiple blood sampling to obtain a full pharmacokinetic profile cannot be proposed in neonates. Population pharmacokinetic analysis, with minimal sampling schemes, is more appropriate but involves more subjects than the traditional approach. Population pharmacokinetic analysis also focuses on the influence of individual factors on pharmacokinetic parameters. Most studies performed with neonates have involved drugs with a narrow safety margin and cleared by renal or metabolic routes to study the impact of immaturity on drug concentrations and on clinical effects.

Humans↗
PubMedDate not supplied

[Clinical relevance of N-acetyltransferase type 2 (NAT2) genetic polymorphism].

Polymorphic N-acetyltransferase (NAT2) is involved in the metabolism of several compounds relevant in pharmacology or toxicology, with diverse clinical consequences. Inter-ethnic variations in distribution of the acetylation phenotype are significant. The caffeine test is most often used to assess the acetylation phenotype and to identify rapid and slow acetylators. The NAT2 phenotype could account for the increased risk of certain side effects in slow acetylators treated with isoniazid (particularly peripheral neuropathies and lupus erythematosus), although therapeutic efficacy seems to be independent of the acetylation status. Hypersensibility reactions with sulfonamides (including Lyell and Stevens-Johnson syndromes) are more frequent in slow acetylators, who also show poor tolerance to sulfasalazine and dapsone. In contrast, myelotoxicity induced by amonafide is more frequent in rapid acetylators, probably because of increased production of a toxic metabolite of the drug. In carcinogenesis, NAT2 may play a protective role against bladder cancer, although studies have shown contradictory results. Slow acetylators may have a risk of developing primitive liver cancer. For lung cancer, data are not conclusive, but slow acetylation status may predispose to mesothelioma in subjects exposed to asbestos. No relation has been found between acetylation phenotype and breast cancer. Contradictory results were reported on its role in colorectal cancer. Non-smoking type 1 diabetics may be at increased risk of nephropathy if they are rapid acetylators. Parkinson's disease may be more frequent among slow acetylators, but again, data have shown contradictory results. Finally, a poor acetylator phenotype may predispose to atopic diseases.

Acetylation↗
PubMedDate not supplied

Extrarenal sorbitol clearance after liver transplantation.

Extrarenal sorbitol clearance was measured in liver transplant patients after a steady-state perfusion. Four measurements were performed in 3 patients with various liver diseases (beginning or patent acute rejection, cytomegalovirus hepatitis, hepatic metastasis). The mean (+/- SD) extrarenal sorbitol clearance was 14.8 +/- 0.1 ml/min.kg. In 5 patients with minimal or no liver abnormalities, the mean from 5 measurements of extrarenal sorbitol clearance was 18.9 +/- 5.0 ml/min.kg. Extrarenal sorbitol clearance values in this later group were higher than the values previously reported in healthy subjects.

Adult↗
PubMedDate not supplied

Effects of liver diseases on drug metabolism.

Although the liver is the main site of drug metabolism, conflicting results have been reported on drug elimination during liver diseases. Drug metabolism may depend on histological changes in the liver (acute or chronic hepatitis, cirrhosis) but may also depend on their origin (viral, toxic or immunological). Drug metabolism is also influenced by the severity of liver dysfunction. Cytochrome P450 isozymes and conjugation pathways may be differently affected by these conditions, and specific probe drugs have to be used in order to study the effect of diseases on each enzyme of drug metabolism. Probe-based assays must be validated during disease, since the pharmacokinetics of the parent drug and/or of its metabolites may be altered. Because of these limitations, therapeutic drug monitoring may be the most reliable way to adjust drug dosing at present.

Cystic Fibrosis↗