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Biomedical subjects

B Moulin

Publications and source records attributed to B Moulin.

87 records · Page 5Linked to original sources
PubMed1987

Pharmacokinetics of habekacin in patients with renal insufficiency.

The pharmacokinetics of habekacin, a new semisynthetic aminoglycoside antibiotic, were investigated in six healthy subjects and 25 uremic patients (six of whom were on hemodialysis) after administration of a single 3-mg/kg dose. Six healthy subjects received the 3-mg/kg dose both intramuscularly (i.m.) and intravenously (i.v.) (1-h infusion). Uremic patients were given the 3-mg/kg dose as an i.m. injection, except for the hemodialysis patients, who received the dose as a 1-h i.v. infusion. After the i.m. injection, the peak concentrations in serum were higher and the times to peak levels were longer in patients with renal impairment than in healthy subjects. The elimination half-life in serum increased in relation to the degree of renal impairment, from 2 h in normal subjects to 32 h in patients with creatinine clearances of less than 10 ml/min. Renal impairment did not significantly modify the apparent volume of distribution. After the same 3-mg/kg dose as a 1-h i.v. infusion in six hemodialysis patients, the elimination half-life averaged 48 and 5 h off and on a 4- to 5-h hemodialysis session, respectively. The habekacin pharmacokinetic data appeared to be similar to those of the other available aminoglycoside antibiotics.

Adult↗
PubMed1987

[Pharmacokinetics of habekacin in patients with chronic renal insufficiency].

Pharmacokinetics of habekacin, a new semisynthetic aminoglycoside antibiotic were investigated in six healthy subjects and twenty-five uraemic patients (six of whom were on hemodialysis) after a single 3 mg/kg Im or IV administration. After the IM injection, the peak serum levels were higher and the times to peak levels were longer in patients with renal impairment than in healthy subjects. Elimination serum half-life increased in relation to the degree of renal impairment, from 2 h in normal subjects to 32 h in patients with creatinine clearance below 10 ml/min. Renal impairment did not significantly modify the apparent volume of distribution. After a single 3 mg/kg dose as one hour-IV infusion in six hemodialysis patients, elimination half-life averaged 48 h and 5 h, out of and on a 4 to 5 hour-hemodialysis session, respectively. Habekacin pharmacokinetic parameters appeared to be similar to those of the other available aminoglycoside antibiotics.

Aminoglycosides↗
PubMed1986

[Renal complications of anti-cancer chemotherapy].

This review is not intended as a complete study of the nephrotoxicity of chemotherapy agents used in the treatment of cancer. The number of these drugs that are cytotoxic has considerably increased in the last few years and our information is incomplete for many of them. We therefore reviewed the observations reported in the literature. Cis-platinum, streptozotocin, methotrexate at high doses, mithramycin and mitomycin are highly nephrotoxic. Other drugs, such as nitrosoureas, celiptium are less nephrotoxic while some appear to rarely induce nephrotoxicity. Anticancer drug nephrotoxicity is characterized by its particular insidiousness, its time of occurrence and its evolution. Since no clinical manifestations accompany the lesions, nephrotoxicity must be sought routinely. It can occur early or late, may be constant as of the first course or appear only after a certain cumulative dose and even occasionally after such a long interval that its cause may appear to be in doubt. The severity of this nephrotoxicity ranges from the usual first minor urinary anomalies to terminal renal failure. The pathophysiogenic mechanisms of the nephrotoxicity remain in most cases obscure. The mode of penetration into the cells is not known. There are fewer data on the interaction between the toxic agent and the cellular metabolism. In most cases, the drug itself in unchanged form does not seem to be the causative agent, which appears rather to be its metabolite. These metabolites are not always identified. Thus nephrotoxicity of antitumoral agents has not been given sufficient attention. Only better knowledge of their action within the kidney will eventually lead to progress in preventing their harmful side effects.

Alkylating Agents↗
PubMed1985

[Prospective study of a triple immunosuppressive combination in renal transplantation: cyclosporin A-corticoids-azathioprine].

Cyclosporin A significantly improves patient and graft survival as compared with the conventional corticosteroid-azathioprine treatment. However, the results are the same, or even worse, when the cyclosporin A-corticosteroid regimen is compared with the corticosteroid-azathioprine-antilymphocyte globulin regimen. The authors have investigated a prednisone-azathioprine-low dose cyclosporin A combination in 46 high risk patients from a series of 117 renal transplantations performed in 1983. The actuarial patient and graft survival rates were as good as, but not better than, those obtained in 1982 in 106 patients treated with the conventional regimen which includes antilymphocyte globulin; they were 96.5% vs 98% and 85.5% vs 84% respectively at 6 months; 96.5% vs 98% and 83.5% vs 84% respectively at 12 months. The low dosage utilized (8 mg/kg instead of the usual 14-17 mg/kg) avoided virtually all the extrarenal side-effects of cyclosporin A, but not its nephrotoxicity. The theoretical risk of excessive immunosuppression was not confirmed by our study. Since cyclosporin A is very expensive, other therapeutic methods for optimal usage of that drug should be investigated.

Azathioprine↗
PubMed1984

The lipid content of the diabetic kidney of the rat.

Rats were made diabetic by intravenous administration of streptozotocin, 100 mg/kg. Six groups of animals were studied: normal; animals given a supplement of 100% corn oil margarine; insulin-treated normoglycemic diabetic; hyperglycemic nonacidotic diabetic; ketoacidotic diabetic; and NH4Cl acidotic. The kidneys were removed from anesthetized animals. The renal cortex was separated from the medulla, freeze-clamped, and homogenized. Total lipids were extracted and measured gravimetrically. Lipid fractions were determined by thin-layer chromatography. Fatty acids of triacylglycerols and of phospholipids were analyzed by gas chromatography. Plasma triacylglycerols were elevated in hyperglycemic nonacidotic rats and more so in ketoacidotic animals. Total kidney lipids were 18% higher in nonacidotic hyperglycemic rats and 56% higher in ketoacidotic diabetic rats. This was due to accumulation of triacylglycerols while the phospholipid and cholesterol fractions did not change. Examination of long-chain fatty acids of kidney cortex triacylglycerols revealed that palmitate rose in a significant fashion while linoleate fell. This pattern was similar in all three groups of diabetic animals. The present data characterize the lipid content of the experimental rat diabetic kidney. They establish that the accumulation of lipids in the renal cortex during diabetes is related to triacyclgycerols and their palmitate content. Our study also provides a clear profile of plasma triacylglycerols during diabetes mellitus in the rat.

Ammonium Chloride↗
PubMed1983

Normal urate transport into erythrocytes in familial renal hypouricemia and in the Dalmatian dog.

It has been hypothesized that humans with familial renal hypouricemia may have a generalized defect of urate transport across cell membranes due to the genetic deletion of a specific carrier, a defect similar to that reported in the Dalmatian dog. In this study the transport of urate labelled with carbon 14 by the erythrocytes of four patients with familial renal hypouricemia was identical to that of five healthy controls. The addition of hypoxanthine to the incubation medium inhibited the transport to a similar extent in the two groups of patients, demonstrating the presence of a carrier specific for urate. This carrier was also found to be present in the erythrocytes of Dalmatian and mongrel dogs. Thus, the renal anomaly causing the hypouricemia in both species is not related to a generalized deletion of a urate-transporting protein on cell membranes.

Animals↗
PubMed1982

Net urate reabsorption in the Dalmatian coach hound with a note on automated measurement of urate in species with low plasma urate.

A progressive reduction of renal blood flow and glomerular filtration rate induced by the stepwise clamping of a Goldblatt clamp increases the urate over creatinine clearance ratio from 1.2 to 1.9 in normal urate-secreting Dalmatian dogs. These clearance data support the existence of a predominant postreabsorptive secretory flux of urate in the normal Dalmatian dog. In contrast, in Dalmatians loaded with pyrazinoic acid which suppresses urate secretion, net reabsorption of urate is unmasked and the urate over creatinine clearance ratio decreases with the progressive reduction in glomerular filtration rate (down to 0.44). It is concluded that the net reabsorption of urate measured by conventional clearance techniques after pharmacologic depression of the urate secretory flux probably reflects true urate reabsorption in the nephron of this species.

Absorption↗
PubMedDate not supplied

Is sirolimus responsible for proteinuria?

Sirolimus (SRL) is suspected to induce proteinuria. We retrospectively studied proteinuria in a population of liver (n = 29) and kidney transplant (n = 30) recipients switched to SRL with progressive diminution or withdrawal of calcineurin inhibitors (CNI). We also observed estimated glomerular filtration rate (GFR), modification of treatment with antiproteinuric drugs, and changes in concentration of SRL. Collection of data started 3 months before SRL introduction at a mean follow-up of 21 months. Following SRL introduction, proteinuria was not detected in the 28 liver transplant patients, and was stable in the two others. In the kidney transplant group, proteinuria did not occur in 12 patients, remained stable in three, and was slightly increased in 14 (0.57 +/- 0.93 g/d vs 1.83 +/- 1.26 g/d). For all patients, eGFR remained stable; there was no difference in management of antiproteinuric drugs. As suspected, cyclosporin (CsA) and tacrolimus (FK) serum concentrations were decreased. We observed a significant correlation between the variation of proteinuria and the variation of serum concentration of CsA or FK (respectively, P = .001 and P = .007). On the other hand, we did not find any correlation between variation in proteinuria and concentration of SRL. This retrospective study suggests that in our cohort of liver transplant patients without previous renal damage, SRL did not provoke proteinuria. On the other hand, the slight aggravation of proteinuria in a subgroup of kidney transplant patients seems to be linked to the hemodynamic renal effects due to CNI withdrawal.

Colforsin↗
PubMedDate not supplied

Comparative regional distribution of angiotensin-I-converting enzyme in the rat, rabbit, dog, monkey and human kidneys.

Kidney is the main source of the production of renin and angiotensin, while also being one of their main target organs. This study was designed to determine the regional distribution of angiotensin-I-converting enzyme (ACE) in the kidney using a biochemical approach. Interspecies variations were analyzed in human, monkey, rabbit, dog and rat kidneys. Kidney ACE content differed among species with decreasing contents as follows: rabbit greater than human greater than monkey greater than dog greater than rat. In rabbit, human, monkey and dog kidneys, we observed predominant cortical distribution of ACE compared with the medulla or papilla; median cortex/papilla ACE activity ratio was 19, 14, 9 and 7 for the rabbit, human, dog and monkey, respectively. In rat kidney, ACE predominantly distributes in the outer medulla, while cortex ACE content appears to be low. The difference in ACE distribution in the rat kidney and to a lesser extent in the dog kidney when compared to rabbit, monkey or man should be taken into account when extrapolating to the human renal hemodynamic studies, which are frequently performed in rats or dogs.

Adult↗