sdz-imm-125 and lauric-acid

sdz-imm-125 has been researched along with lauric-acid* in 1 studies

Other Studies

1 other study(ies) available for sdz-imm-125 and lauric-acid

Article	Year
Hydroxyethyl cyclosporin A induces and decreases P4503A and P-glycoprotein levels in rat liver. Xenobiotica; the fate of foreign compounds in biological systems, 1996, Volume: 26, Issue:1 1. A new immunosuppressant SDZ IMM 125 (IMM), the hydroxyethyl derivative of D-serine8-cyclosporin (cyclosporin A, CSA), induced or decreased the liver P450s of rat, in particular the 3A proteins, depending on the dose and duration of exposure. Doses of 20 mg/kg/day for 2 weeks and 10 mg/kg/day for 26 weeks induced the rat liver 3A levels 2- and 1.8-fold respectively, whereas 52 weeks of 24 mg/kg/day decreased the 3A levels by 22%. High doses of IMM, 100 mg/kg/day for 26 weeks, significantly decreased the 3A levels by 56%. 2. Changes in the rate of IMM biotransformation paralleled the changes in the levels of liver 3A indicating that liver 3A levels could influence the clearance of IMM. 3. Both IMM and CSA affected liver and kidney P-glycoprotein (Pgp) levels. The increases measured after short-term treatment (20 mg/kg/day for 2 weeks) in the liver (1.8-fold) and kidney (1.3-fold) were less pronounced in the long-term studies in which liver Pgp levels were increased 1.4-fold (48 mg/kg/day for 52 weeks). At higher doses (100 mg/kg/day for 26 weeks) Pgp levels were significantly decreased. The modulation of Pgp levels by IMM did not parallel the changes in 3A levels, indicating that Pgp regulation is most likely due to a direct effect of the cyclosporin rather than a co-regulation mechanism linked to 3A or P4501A modulation. 4. Increased arachidonic metabolism to the 19- and 20-HETE metabolites, a possible mechanism of the cyclosporin-induced renal hypertension, occurred in the liver microsomes and not the kidney S9 fraction of the 2-week study, and only at very high doses (100 mg/kg/day) in the longer studies (26 weeks). Topics: Animals; Arachidonic Acid; ATP Binding Cassette Transporter, Subfamily B, Member 1; Biotransformation; Cyclosporins; Cytochrome P-450 CYP3A; Cytochrome P-450 Enzyme System; Enzyme Induction; Immunoblotting; Immunosuppressive Agents; In Vitro Techniques; Kidney; Lauric Acids; Liver; Male; Mixed Function Oxygenases; Oxidation-Reduction; Rats; Rats, Wistar; Subcellular Fractions	1996

Article

Year

Hydroxyethyl cyclosporin A induces and decreases P4503A and P-glycoprotein levels in rat liver.

Xenobiotica; the fate of foreign compounds in biological systems, 1996, Volume: 26, Issue:1

1. A new immunosuppressant SDZ IMM 125 (IMM), the hydroxyethyl derivative of D-serine8-cyclosporin (cyclosporin A, CSA), induced or decreased the liver P450s of rat, in particular the 3A proteins, depending on the dose and duration of exposure. Doses of 20 mg/kg/day for 2 weeks and 10 mg/kg/day for 26 weeks induced the rat liver 3A levels 2- and 1.8-fold respectively, whereas 52 weeks of 24 mg/kg/day decreased the 3A levels by 22%. High doses of IMM, 100 mg/kg/day for 26 weeks, significantly decreased the 3A levels by 56%. 2. Changes in the rate of IMM biotransformation paralleled the changes in the levels of liver 3A indicating that liver 3A levels could influence the clearance of IMM. 3. Both IMM and CSA affected liver and kidney P-glycoprotein (Pgp) levels. The increases measured after short-term treatment (20 mg/kg/day for 2 weeks) in the liver (1.8-fold) and kidney (1.3-fold) were less pronounced in the long-term studies in which liver Pgp levels were increased 1.4-fold (48 mg/kg/day for 52 weeks). At higher doses (100 mg/kg/day for 26 weeks) Pgp levels were significantly decreased. The modulation of Pgp levels by IMM did not parallel the changes in 3A levels, indicating that Pgp regulation is most likely due to a direct effect of the cyclosporin rather than a co-regulation mechanism linked to 3A or P4501A modulation. 4. Increased arachidonic metabolism to the 19- and 20-HETE metabolites, a possible mechanism of the cyclosporin-induced renal hypertension, occurred in the liver microsomes and not the kidney S9 fraction of the 2-week study, and only at very high doses (100 mg/kg/day) in the longer studies (26 weeks).

Topics: Animals; Arachidonic Acid; ATP Binding Cassette Transporter, Subfamily B, Member 1; Biotransformation; Cyclosporins; Cytochrome P-450 CYP3A; Cytochrome P-450 Enzyme System; Enzyme Induction; Immunoblotting; Immunosuppressive Agents; In Vitro Techniques; Kidney; Lauric Acids; Liver; Male; Mixed Function Oxygenases; Oxidation-Reduction; Rats; Rats, Wistar; Subcellular Fractions

1996