Biomedical subjects

S Urien

Publications and source records attributed to S Urien.

112 records · Page 7Linked to original sources

PubMedDate not supplied

Binding of anthracycline derivatives to human serum lipoproteins.

The binding of eight anthracycline analogues (including mitoxantrone) to isolated serum lipoproteins (high, low and very low density lipoproteins) was studied in order to elucidate some determinants of their interaction with lipidic structures. Serum lipoproteins were isolated by ultracentrifugation. Drug binding experiments were run by ultrafiltration at 37 degrees C and pH 7.4. Anthracycline concentrations (total and free) were determined by HPLC with fluorometric detection. All the ligands were significantly bound to the three lipoprotein classes, and for each ligand the binding increased as the lipidic fraction of lipoprotein increased. From doxorubicin to iododoxorubicin, there was a tenfold increase in lipoprotein binding (doxorubicin < mitoxantrone < epirubicin < daunorubicin < pirarubicin < aclarubicin < zorubicin < iododoxorubicin). For all the ligands studied, the extent of lipoprotein binding appears to be related to chemical determinants of lipophilicity.

Antibiotics, Antineoplastic↗

PubMedDate not supplied

Evaluation of two dose individualisation methods for carboplatin.

The pharmacokinetics of carboplatin are usually evaluated by measuring plasma concentrations of ultrafiltered platinum (UP). This approach, however may be less reliable than measuring the plasma concentration of total platinum (TP). In a group of 14 patients, which constituted a reference group, the clearance of TP was highly correlated with creatinine clearance, as estimated by the method of Cockroft and Gault. This relationship, together with only morphological and biological parameters, was used to estimate TP clearance, Vc and AUC, in a validation group of 8 patients. Estimated TP clearance was 97.9 +/- 18% of the actual value. The TP pharmacokinetic parameters of the reference group were used to estimate those of the validation group, using only two or three plasma concentration measurements (Bayesian approach). With the Bayesian approach, the estimated TP clearance was up to 99.9 +/- 2.7% of the actual value. In conclusion, estimation of TP pharmacokinetics may be reliably estimated as an alternative to UP in clinical practice.

Adult↗

PubMedDate not supplied

[Value of protecting mitochondrial functions during treatment with cyclosporin A].

The use of cyclosporin A is often limited by its nephrotoxicity. This dose-dependent toxicity can occur in all kinds of transplantation and is reversed with drug withdrawal. Cyclosporin A induces a vasoconstriction leading to an increase of renal vascular resistance and a reduction of glomerular filtration. Histochemical studies show mitochondrial alterations and an excess of cytosolic and mitochondrial calcium leading to a decrease of ATP synthesis. Two strategies can be evoked for limiting cyclosporin-A-induced nephrotoxicity. First, the use of drugs counteracting the vasoconstriction has been proposed. Second, drugs acting by restoration of ATP synthesis could also be of interest. For example, calcium channel blockers may be used for limiting the Ca2+ fluxes into cells. Another way to protect ATP synthesis is to inhibit the cyclosporin-A-induced increase of mitochondrial Ca2+ concentrations; Trimetazidine has shown its efficiency in vitro for protecting mitochondria against these modifications of Ca2+ homeostasis and is under clinical evaluation.

Animals↗

PubMedDate not supplied

[Mediators involved in the nephrotoxicity of cyclosporin A].

Cyclosporin A-induced nephrotoxicity is a well known adverse effect but its mechanism remains unclear. The understanding of the toxicity mechanism is necessary since the new generation of immunosuppressant drugs (cyclosporin G, FK 506, rapamycin) demonstrates renal toxicity. A renal vasoconstriction occurs with the first administration of cyclosporin and involves several mediators (prostaglandins, renal sympathetic nerves, dopamine. NO, endothelin) which may explain the limited benefit of antagonists. Furthermore, the vasoconstriction explains only haemodynamic modifications and cannot explain histological lesions. New hypotheses involving an alternation of cellular calcium homeostasis suggest alternative investigations to elucidate cyclosporin A nephrotoxicity.

Adjuvants, Immunologic↗