A Radioimmunoassay to Measure Cyclosporin a in Plasma and Serum Samples

Donatsch, P.; Abisch, E.; Homberger, M.; Traber, René; Trapp, Márcia; Voges, Raphael

doi:10.1080/01971528108062989

Cited by 268 publications

(39 citation statements)

References 6 publications

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“…measurements has been reported previously (Donatsch et al, 1981;Carruthers et al, 1983;Kennedy et al, 1984). Based on RIA studies with serum, Donatsch et al (1981) attributed this to the cross reactivity of metabolite 17 with the cyclosporin antibody.…”

Section: Discussionmentioning

confidence: 70%

“…Based on RIA studies with serum, Donatsch et al (1981) attributed this to the cross reactivity of metabolite 17 with the cyclosporin antibody. However, since we found essentially no metabolite 17 or 18 in serum, the differences between RIA and h.p.l.c.…”

Section: Discussionmentioning

confidence: 99%

“…(Carruthers et al, 1983) and RIA (Donatsch et al, 1981). The limits of detection for cyclosporin by h.p.l.c.…”

Section: Methodsmentioning

confidence: 99%

“…Metabolite 17 Several cyclosporin metabolites have been identified by chromatography (Beveridge, 1981). Two major oxidative metabolites, 17 and 18, have been isolated from urine (Donatsch et al, 1981;Neiderberger, personal communication). Metabolite 17 is formed by hydroxylation of amino acid 1 and metabolite 18 contains both a hydroxyl group and a cyclic ether in the side chain of amino acid 1 (Figure 1).…”

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confidence: 99%

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

Freeman¹,

Laupacis²,

Pa³

et al. 1984

Brit J Clinical Pharma

101

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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.

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Section: Discussionmentioning

confidence: 70%

Section: Discussionmentioning

confidence: 99%

“…(Carruthers et al, 1983) and RIA (Donatsch et al, 1981). The limits of detection for cyclosporin by h.p.l.c.…”

Section: Methodsmentioning

confidence: 99%

mentioning

confidence: 99%

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

Freeman¹,

Laupacis²,

Pa³

et al. 1984

Brit J Clinical Pharma

101

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“…Initially, CsA analysis was based on radioimmunoassay (r.i.a. ), which uses a rabbit polyclonal antibody, which cross-reacts to a large extent with metabolites of CsA (Donatsch et al, 1981;Robinson et al, 1983). Some of the metabolites may have weak immunosuppressive properties, while others appear to be inactive (Freed et al, 1987;Hartman & Jardine, 1987;Hartman et al, 1985;Maurer, 1985).…”

Section: Introductionmentioning

confidence: 99%

A prospective study of cyclosporine concentration in relation to its therapeutic effect and toxicity after renal transplantation.

Lindholm¹,

Dahlqvist²,

Groth³

et al. 1990

Brit J Clinical Pharma

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1. Cyclosporine (CsA) concentrations in plasma and whole blood were monitored prospectively in 66 consecutive kidney transplant recipients for 6 months after transplantation or until graft loss. Immunosuppression was based on treatment with CsA and prednisolone in 27 patients and CsA, azathioprine and prednisolone in 39 patients. 2. Whole blood and plasma samples (separated at 37 degrees C) were collected 10‐12 h after CsA dosage twice weekly over the first 3 months and thereafter once weekly. CsA concentrations were measured by high pressure liquid chromatography (h.p.l.c.) in plasma, by specific and non‐specific monoclonal radioimmunoassays (r.i.a.) in whole blood, and by polyclonal r.i.a. and polyclonal fluorescence polarization immunoassay (f.p.i.a.) in whole blood and plasma. 3. There were no differences between the treatment schedules regarding graft or patient survival, occurrence of acute rejection, nephrotoxicity or infection. 4. CsA concentrations were significantly lower at the time of acute rejection than one week earlier based on all of the analytical methods used except f.p.i.a. 5. The lowest CsA concentration, recorded during the first month after transplantation, was significantly lower in patients with than in patients without experience of acute rejection episodes when the CsA concentrations were measured by polyclonal r.i.a. in whole blood and plasma and by specific and non‐specific monoclonal r.i.a. in whole blood, but not by h.p.l.c. in plasma or polyclonal f.p.i.a. in whole blood or plasma. 6. The highest CsA concentration recorded during the second post‐transplantation month, was higher in patients with acute nephrotoxicity than in those without nephrotoxicity when CsA was measured by specific monoclonal r.i.a. in whole blood (471 +/− 409 ng ml‐1 vs 327 +/− 150 ng ml‐1, P less than 0.05), but not by the other methods. 7. The mean plasma h.p.l.c. concentration of CsA measured by h.p.l.c. during the first month after transplantation was significantly higher in patients who suffered from systemic infection than in patients who did not (116 +/− 70 ng ml‐1 vs 82 +/− 52 ng ml‐1; P less than 0.05). 8. Thus, significant relationships between CsA concentrations and clinical events were apparent using assay methods specific for CsA as well as using polyclonal r.i.a., but not using polyclonal f.p.i.a. When h.p.l.c. was used, however, plasma drug concentrations were often below the limit of determination. Our results suggest that specific analysis of CsA in whole blood allows the best distinction between patients who respond favourably and less favourably to treatment with CsA.

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Renal Interstitial Fibrosis and Vascular Changes

Svenson¹

1986

Arch Intern Med

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A Radioimmunoassay to Measure Cyclosporin a in Plasma and Serum Samples

Cited by 268 publications

References 6 publications

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

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

A prospective study of cyclosporine concentration in relation to its therapeutic effect and toxicity after renal transplantation.

Renal Interstitial Fibrosis and Vascular Changes

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