Intravenous cyclosporine kinetics in renal failure

Follath, F.; Wenk, Markus R.; Vozeh, S; Thiel, G; Brunner, Felix; Loertscher, Rolf; Lemaire, Michel; Nussbaumer, Kurt; Niederberger, Werner; Wood, A. K. W.

doi:10.1038/clpt.1983.226

Cited by 84 publications

(22 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This is consistent with the fact that approximately 50% of cyclosporin in whole blood is taken up by the red blood cell (Beveridge, 1982;Follath et al, 1983), a process which appears to be temperaturedependent (Follath et al, 1983).…”

Section: Discussionsupporting

confidence: 60%

Evaluation of cyclosporin‐phenytoin interaction with observations on cyclosporin metabolites.

Freeman¹,

Laupacis²,

Pa³

et al. 1984

Brit J Clinical Pharma

102

View full text Add to dashboard Cite

We have observed that patients on concurrent cyclosporin and phenytoin therapy required increased doses of cyclosporin to maintain therapeutic concentrations of this novel immunosuppressive drug. We have, therefore, studied the influence of phenytoin on the pharmacokinetics of oral cyclosporin in six healthy male subjects. Cyclosporin concentrations in serum and whole blood were measured by high pressure liquid chromatography (h.p.l.c.) and radioimmunoassay (RIA). Concentrations of cyclosporin in whole blood were consistently higher than corresponding values in serum. Concentrations of cyclosporin determined by RIA were also consistently higher than those determined by h.p.l.c. Irrespective of the biological fluid (serum or whole blood) or the type of drug analysis (h.p.l.c. or RIA), changes in cyclosporin kinetics following phenytoin administration exhibited similar patterns. Phenytoin significantly reduced the maximum concentration and the area under the concentration‐time curve and significantly increased total body clearance of cyclosporin. There was a statistically significant reduction of cyclosporin half‐life (t 1/2) in whole blood using h.p.l.c. analysis. However, there was no significant change in cyclosporin t 1/2 in serum following phenytoin administration, using either form of drug analysis. Cyclosporin metabolites 17 and 18 were measured by h.p.l.c. in whole blood samples only, since these metabolites were found almost entirely in red blood cells. Phenytoin significantly reduced the Cmax and AUC of both metabolites, but no significant change was observed in the t 1/2 of either. Phenytoin enhanced the metabolism of antipyrine which was co‐administered with cyclosporin to assess oxidative enzyme activity. We conclude that patients undergoing organ transplantation should be carefully monitored if they require phenytoin or other drugs known to accelerate oxidative metabolism.

show abstract

Section: Discussionsupporting

confidence: 60%

Evaluation of cyclosporin‐phenytoin interaction with observations on cyclosporin metabolites.

Freeman¹,

Laupacis²,

Pa³

et al. 1984

Brit J Clinical Pharma

102

View full text Add to dashboard Cite

show abstract

“…The other disposition kinetic parameters (V1, A1, X2, Cl') all agreed with those obtained previously (Gupta et al, 1987); while the value of Vs (4.331 kg-l) is similar to that of 3.51 kg-l reported by Follath et al (1983), in renal transplant patients.…”

Section: Discussionsupporting

confidence: 81%

Pharmacokinetics of cyclosporin: influence of rate‐duration profile of an intravenous infusion in renal transplant patients.

Gupta

Bakran

Johnson

et al. 1989

Brit J Clinical Pharma

View full text Add to dashboard Cite

show abstract

“…1. Because the maximum blood concentrations (C max ) of cyclosporine after intravenous or oral dosing are more than 20 times higher than those of tacrolimus, [21][22][23][24][25] the inhibitory eŠects of 20 mM cyclosporine was also estimated. Cyclosporine and tacrolimus neither inhibited nor stimulated any of the metabolic activities except that 20 mM cyclosporine inhibited CYP2C19 and CYP2D6 activities by 29％ and 30％, respectively, and that both cyclosporine and tacrolimus inhibited CYP3A4-mediated nifedipine oxidation and testosterone 6b-hydroxylation activities.…”

Section: Resultsmentioning

confidence: 99%

Effect of Cyclosporine and Tacrolimus on Cytochrome P450 Activities in Human Liver Microsomes

et al. 2007

View full text Add to dashboard Cite

The eŠects of cyclosporine and tacrolimus on cytochrome P450 (CYP) 1A2-mediated 7-ethoxyresoruˆn O-deethylation, CYP2C9-mediated tolbutamide hydroxylation, CYP2C19-mediated S-mephenytoin 4′ -hydroxylation, CYP2D6-mediated debrisoquine 4-hydroxylation, CYP2E1-mediated chlorzoxazone 6-hydroxylation, CYP3A4-mediated nifedipine oxidation, and CYP3A4-mediated testosterone 6b-hydroxylation activities in human liver microsomes were compared. Cyclosporine and tacrolimus, at concentrations of 0.2 or 2 mM, neither inhibited nor stimulated any of the metabolic activities except for those of CYP3A4. On the other hand, cyclosporine and tacrolimus competitively inhibited CYP3A4-mediated nifedipine oxidation activity, with inhibition constants (K i ) of 1.42 and 0.36 mM, respectively. In addition, 20 mM cyclosporine inhibited CYP2C19 and CYP2D6 activities by 29％ and 30％, respectively. These results suggest that tacrolimus would not cause clinically signiˆcant interactions with other drugs, which are metabolized by CYPs, via the inhibition of hepatic metabolism and that the reason why cyclosporine, but not tacrolimus, has a pharmacokinetic inhibitory eŠect might be that the dosage and/or the unbound concentrations around its metabolic enzymes are higher than those of tacrolimus, rather than the diŠerences in the inhibition potential. Obvious substrate-dependent eŠects on CYP3A4-inhibition potential were not observed.

show abstract

Intravenous cyclosporine kinetics in renal failure

Cited by 84 publications

References 0 publications

Evaluation of cyclosporin‐phenytoin interaction with observations on cyclosporin metabolites.

Evaluation of cyclosporin‐phenytoin interaction with observations on cyclosporin metabolites.

Pharmacokinetics of cyclosporin: influence of rate‐duration profile of an intravenous infusion in renal transplant patients.

Effect of Cyclosporine and Tacrolimus on Cytochrome P450 Activities in Human Liver Microsomes

Contact Info

Product

Resources

About