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Biomedical subjects

B Moulin

Publications and source records attributed to B Moulin.

At least 73 records · Page 4Linked to original sources
PubMed1990

[Pharmacokinetics and the aged person].

Visceral insufficiencies appeared or might be more important with age, thus it is not surprising to note pharmacokinetic alterations in elderly subjects. There are several age related changes in gastrointestinal function that might alter absorption of drugs. Gastric acid secretion and motility both decline with age. Intestinal surface and blood flow also diminished. But the effect of these changes is far eclipsed by other factors. The plasma-binding proteins diminish. The intracorporeal distribution of drugs is modified in elderly subjects. Total body weight and especially lean body mass is reduced: thus higher plasma levels of drug result. Hepatic clearance is in relation to liver mass and hepatic blood flow, both of which diminish with age. Hepatic enzymatic function, particularly oxidative process, is also decreased. The most important modification is a reduced excretion of drugs. Renal blood flow, glomerular filtration rate are decreased and these alterations may induce an accumulation of drugs or metabolites. Thus, it is necessary to be cautious when we prescribe drugs to elderly patients. We recommended to give small dosage and to increase dosage progressively. It is also necessary to pay attention to clinical or biological signs of intolerance in these subjects.

Aged↗
PubMed1990

Atrial natriuretic peptide in the renal response to an acute protein load.

A high protein meal acutely stimulates the glomerular filtration rate. In order to assess the possible role of atrial natriuretic peptide (ANP) as a mediator of this renal response, the ANP plasma concentrations were measured with a sensitive radioimmunoassay method before and after a large protein load (1.5 g/kg body weight given as a meat meal). Creatinine clearance increased significantly while fractional excretion of sodium remained constant. ANP plasma concentrations did not change after the protein load and the intra-individual variations of creatinine clearance were not correlated with the intra-individual changes in ANP plasma concentrations. It was concluded that ANP was probably not involved in the renal haemodynamic changes observed after a large protein load.

Adult↗
PubMed1989

Aetiology of nephrotoxic damage to the renal interstitium and tubuli.

The kidney is particularly susceptible to the deleterious effects of drugs, and drug-induced nephropathies are now fairly well understood. All the components of the renal parenchyma can be affected, but we have focused our attention on tubulointerstitial nephropathies. All of the pathophysiological mechanisms are not known, but it is possible to describe two types of renal alteration. The first is due to a direct toxic action by, for example, antibiotics, contrast media, nonsteroidal antiinflammatory agents, antalgics and analgesics. The second type of alteration appears to be due to immunoallergic reactions to, for instance, penicillin and its derivatives, rifampin, sulphonamides and phenindione. We also underline the risk factors that favour the occurrence of renal complications and the means that can be used to prevent them.

Acute Kidney Injury↗
PubMed1989

Pharmacokinetics of cilazapril in patients with renal failure.

1. The pharmacokinetics of a single 1 mg dose of cilazapril were determined in six subjects with normal renal function and in 19 uraemic patients with various degrees of renal impairment. 2. Significant decreases in systolic and diastolic blood pressure were noted in all groups of subjects between 2 and 8 h after administration of 1 mg cilazapril. 3. There was a significant correlation between ACE inhibition at 24 h and creatinine clearance (CrCL). 4. For cilazapril, Cmax and tmax were independent of creatinine clearance. AUC(24) was inversely related to CrCL and apparent plasma clearance (CL/F) was directly related to CrCL. 5. For cilazaprilat, Cmax and tmax were related to creatinine clearance. AUC(24) was inversely related to CrCl and apparent plasma clearance (CL/F) was directly related to CrCL. 6. Dialysis clearance was approximately 2 l h-1 for cilazapril and for cilazaprilat. 7. The effects of renal impairment on cilazapril and cilazaprilat kinetics were similar to those observed for other inhibitors of angiotensin-converting enzyme such as captopril, enalapril and lisinopril. 8. It may be necessary to modify doses of cilazapril for the treatment of essential hypertension in uraemic patients. When creatinine clearance was below 15 ml min-1 cilazaprilat concentrations were increased, half-lives were prolonged and ACE inhibition remained above 90% for at least 24 h. A reduced dosage is indicated for these patients. 9. In patients requiring haemodialysis, maintenance doses of 0.5 mg given after each haemodialysis session are sufficient.

Adult↗
PubMed1989

Recurrent essential mixed cryoglobulinemia in renal allografts. Report of two cases and review of the literature.

This report describes two patients in whom essential IgG-IgM mixed cryoglobulinemia (EMC) glomerulonephritis led to end-stage renal disease. Both patients underwent primary hemodialysis, and during the period of uremia clinical and biological manifestations of the disease fully resolved. Transplantation was performed, and in both cases cryoglobulinemia quickly recurred (30 days and 6 months after transplantation, respectively) with clinical renal and extrarenal flare, and reappearance of the biological markers of the disease (decrease in C3 and C4 components of serum complement, detection of rheumatoid activity and of cryoglobulinemia in the serum). The literature on EMC glomerulonephritis leading to end-stage renal disease is reviewed. Factors that may have contributed to extinguishing the disease and to further recurrence following transplantation-consequences of uremic state, alloimmunization and intercurrent infectious disease-are discussed.

Adult↗
PubMed1989

High affinity binding sites for Perindopril a new inhibitor of angiotensin-I-converting enzyme (ACE) in the rabbit kidney: possible evidence for localization of ACE in endothelial structures and in glomerular mesangium.

The tissue distribution of Perindopril, a new potent inhibitor of the angiotensin-converting enzyme (ACE), was studied after in vivo intravenous injection into rabbits of tracer amounts of the tritiated drug either alone (no modification of the renin angiotensin system) or along with a pharmacologic dose of 10 mg/kg unlabelled Perindopril. Lung and kidneys were the most densely labelled tissues. Kidney distribution of tritiated Perindopril was studied either by histo-autoradiography or by measurement of radioactivity in the homogenates of dissected kidney zones. A close parallelism was found between the distribution patterns of ACE and radioactivity throughout the kidney. Tritiated-Perindopril binding was inhibited by concurrent treatment of the animals with the unlabelled drug or pretreatment with Captopril. Autoradiographic study of kidney slices after the administration of tracer amounts of Perindopril showed an intense labelling of the glomerular mesangium and of endothelial structures of blood vessels, and a lack of labelling of tubular epithelial cells. The possible occurrence of two pools of "ACE-like" activity in the kidney is discussed, namely i) one pool which is labelled by tritiated Perindopril, located in glomerular mesangium and endothelial structures which may be involved in the pharmacological action of ACE inhibitors; and ii) a second pool located in the proximal-tubule cell brush-border, remaining unlabelled by Perindopril, for which the high amount of neutral endopeptidase present at this site may be responsible.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1989

[Drug-induced nephropathies].

The list of nephrotoxic drugs is long. The kidney is particularly susceptible to the nephrotoxic action of drugs, because of its functional properties, including: a) the high volume of renal blood flow, which brings large amounts of toxin; b) the large area in contact with the drug, either in the glomerulus or the tubule epithelium, which enables toxin interaction or uptake; c) the kidney's ability to transfer active substances, which provides specific transfer mechanisms that mediate cellular uptake; d) drug breakdown, which may occur in renal tubules and lead to the formation of toxic metabolites from non-toxic parent substances; e) the kidney's concentrating mechanisms, which can increase urinary and interstitial concentrations of non-absorbed products; f) the high metabolic rate of tubule cells required for normal function, which is subject to perturbation. Indeed, nephrotoxins affect every aspect of renal pathology, from acute renal failure due to functional alterations to that resulting from tubule cell necrosis. These anomalies may occur suddenly or after a long period of exposure to the toxic agent. They may be localized in the cortex or the medulla and affect all parts of the nephron: the glomeruli, the tubules, the interstitium or the vessels. How then is the topic of a brief expose to be chosen? It was made based upon the results of a questionnaire addressed to French nephrologists.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1989

[Pharmacokinetics of cyclosporin A in patients with nephrotic syndrome].

The pharmacokinetics of Cy A have been studied in patients with N.S.. Eight patients (7 M, 1 F) received a single 12.5 mg/kg oral dose and a single 4 mg/kg intravenous dose. Plasma was separated from red blood cells at 22 degrees C, at least 2 hr after drawing. Cy A plasma levels were determined by reverse HPLC. The comparison of our pharmacokinetic parameters for the oral route with those from reference patients showed significant differences for T1/2 Ka and Tmax which were decreased in N.S. For the I.V. route we found a decrease in total plasma clearance (CLTP). Absolute bioavailability (18%) was also diminished. Moreover total cholesterol and B apolipoprotein were increased in our nephrotic population. Cy A is highly bound to lipoprotein and we found a significant negative correlation between CLTP of Cy A and either B apolipoprotein or total cholesterol. We conclude that the increase of lipoprotein in N.S. is probably responsible of the modifications in pharmacokinetics of Cy A. Nevertheless Cy A dosage can be not modified in N.S. when oral route is used and divided by a factor two for the I.V. route.

Adult↗
PubMed1988

Comparative pharmacokinetics of tromethamine fosfomycin and calcium fosfomycin in young and elderly adults.

The pharmacokinetics of two oral forms of fosfomycin, tromethamine (trometamol) salt and calcium salt, were studied in five young (age, 29 +/- 3 [standard deviation] years) and eight elderly (age, 72 +/- 6 years) adults. The subjects received a single 40-mg/kg (body weight) (approximately equal to 3-g) calcium fosfomycin dose and a 25-mg/kg (approximately equal to 2-g) tromethamine fosfomycin dose in fosfomycin acid form. Blood and urine samples were collected for 24 h. Antibiotic concentrations in serum and urine were measured by microbiological assay. In all subjects, the peak levels of the calcium salt in serum were two- to fourfold lower than those of the tromethamine salt (6 to 7 and 18 to 22 micrograms/ml, respectively), indicating poor intestinal absorption of the calcium form. The elimination half-life of the two oral forms was about 5 h in young adults, and the half-life was only moderately longer in elderly subjects, with large individual variations: 8.28 +/- 5.51 h for tromethamine fosfomycin and 11.80 +/- 6.86 h for calcium fosfomycin. In elderly subjects, absorption of the tromethamine salt form was not modified, but the time to peak level was delayed for the calcium salt (2.58 +/- 0.54 h versus 1.41 +/- 0.67 h in young adults). Pharmacokinetic elimination of the two forms of fosfomycin was only moderately affected in elderly subjects; we observed lower urinary elimination, about 58 versus 28% of the dose in 24-h urines for the tromethamine salt and decreased renal clearance of both forms. However, the dosages of tromethamine and calcium fosfomycin need not be adjusted for elderly subjects who have endogenous creatinine clearances above 50 ml/min per 1.73 m2.

Adult↗
PubMed1988

Is apalcillin nephrotoxic?

Apalcillin is a new semisynthetic penicillin used as a sodium salt. More than 4,000 patients have been treated with this antibiotic, but increased serum creatinine levels were noted in 18 cases. In 5 of these cases, apalcillin was possibly responsible, and in 13 it was doubtful. We decided to study renal function of normal volunteers treated with 4 g of apalcillin. Three periods were studied: a pretreatment control period of 80 min followed by a treatment period of 60 min and a posttreatment period of 40 min. Inulin and p-aminohippurate (PAH) infusion were continued during all three periods. At the beginning of the treatment period, 2 g of apalcillin was injected as a bolus, followed by infusion of 2 g of apalcillin over 1 h. Urinary volume was measured every 20 min. Creatinine, insulin, and PAH clearances and urinary excretion of sodium, potassium, calcium, and magnesium were calculated for each period. Urinary beta-2-microglobulin excretion was also assessed. Analysis of variance was done. We observed no variation in clearances of creatinine or inulin or in urinary electrolyte output. PAH clearance was significantly decreased during apalcillin infusion. Apalcillin appeared to compete with PAH for proximal tubular secretion but induced no further renal dysfunction.

Ampicillin↗
PubMed1988

[Apalcillin and renal function].

Apalcilline is a new semi-synthetic penicillin. More than 4,000 patients were treated with this antibiotic but an increase level of serum creatinine was noted in 18 cases. Responsibility of apalcilline in this side effect could be possible in 5 cases, doubtful in 13 cases. We decided to study renal function of normal volunteers treated with 4 gr apalcilline. Three periods were realised: a control period (80 min), a treatment period (60 min), a post-treatment period (40 min). Inulin and PAH infusion lasted during all these three periods. After the control period 2 gr apalcilline was injected as a bolus followed by a 2 gr apalcilline perfusion for one hour. Urinary volume was measured every 20 min. Creatinine, inulin, PAH clearances, sodium, potassium, calcium, magnesium urinary excretion were calculated for each period. Urinary B2-microglobulin excretion was also appreciated. Analysis of variance was done. We did not observe any variation of creatinine, inulin clearances or variation of urinary electrolytes output PAH clearance was significantly decreased during alpacilline infusion. Apalcilline seems competitive with PAH for proximal tubular secretion. Nevertheless apalcilline did not induce any more renal dysfunction.

Adult↗
PubMed1988

[Pharmacokinetics of trometamol-fosfomycin in patients with renal insufficiency].

Trometamol fosfomycin is a new form of fosfomycin used orally. We have studied pharmacokinetics of this antibiotic in 23 uraemic patients with various degrees of renal insufficiency. The control group was 5 young adult males with a creatinine clearance of 127 +/- 20 ml/mn. All subjects received a single oral dose of 25 mg/kg trometamol fosfomycin. Serum and urine concentrations of fosfomycin were assayed by a microbiological method. Cmax, tmax, AUC were significantly higher in uraemic patients than in normal subjects. t 1/2 beta were prolonged in uraemic patients. Thus it is necessary to modify usual dose regimen when creatinine clearance is below 50 ml/mn.

Administration, Oral↗
PubMed1988

Gallium67 scintigraphy in the diagnosis of glomerulonephritis.

To assess the role of gallium-67 (67Ga) scintigraphy in the diagnosis of glomerular diseases, we performed the following technique in 39 patients with glomerulonephritis (GN) who underwent simultaneous Ga scan and histologic examination. 72 hours after IV injection of Ga citrate (2 mCi), isotopic kidney activity (normally undetectable) was compared to the activity of the liver and quantified as follows: less than (1+), equal to (2+) or greater than (3+) that of the liver. Renal biopsy was performed at the same time to evaluate the type of the GN and to quantify interstitial cellular infiltration. Proteinuria, serum albumin and creatinine were measured. There was a significant correlation between the level of 67Ga kidney activity and the degree of proteinuria and hypoalbuminemia. On the contrary, no correlation was found between isotopic activity and the degree of renal failure or the degree of interstitial cellular infiltration. Increased kidney 67Ga activity did not appear characteristic of a specific histologic type of GN. Increased glomerular permeability may alter renal uptake of Ga; therefore 67Ga scanning does not appear to contribute significantly to the diagnosis and the follow-up of either primary or secondary GN.

Biopsy↗