Clinical Chemistry AACC Online Job Center
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

Clinical Chemistry 49: 1891-1899, 2003; 10.1373/clinchem.2003.021725
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Submit an electronic Letter to
the Editor about this paper
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in ISI Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via ISI Web of Science (10)
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Millán, O.
Right arrow Articles by Martorell, J.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Millán, O.
Right arrow Articles by Martorell, J.
Related Collections
Right arrow Clinical Immunology
Right arrow Drug Monitoring and Toxicology
(Clinical Chemistry. 2003;49:1891-1899.)
© 2003 American Association for Clinical Chemistry, Inc.

Drug Monitoring and Toxicology

Pharmacodynamic Approach to Immunosuppressive Therapies Using Calcineurin Inhibitors and Mycophenolate Mofetil

Olga Millán1, Mercè Brunet2, Josep M. Campistol3, Ana Faura3, Isabel Rojo1, Elena Vidal2, Olga Jiménez2, Jordi Vives1, Federic Oppenheimer3 and Jaume Martorell1,a

1 Servei Immunologia,
2 Servei de Toxicologia, and
3 Unitat de Trasplantament Renal, IDIBAPS, Hospital Clínic de Barcelona, 08036 Barcelona, Spain.

aAddress correspondence to this author at: Hospital Clínic Servei Immunologia, C/Villarroel 170, 08036 Barcelona, Spain. Fax 34-934518038; e-mail jmarto{at}clinic.ub.es.

Background: Graft survival depends on adequate immunosuppression. To evaluate the effect on the immune system of immunosuppressive therapies using calcineurin inhibitors (CNIs), several pharmacodynamic indices have been proposed to complement pharmacokinetic data. In this preliminary study we compared some of these parameters during combined immunosuppressant therapies.

Methods: We treated 65 stable renal transplant recipients with cyclosporin A (CsA; n = 16), tacrolimus (TRL; n = 10); CsA + mycophenolate mofetil (MMF; n = 14); TRL + MMF (n = 13), and MMF (n = 12). Twelve nontreated healthy controls were also included. Calcineurin activity (CNA) in peripheral blood mononuclear cells was measured using 32P-labeled peptide. Interleukin-2 (IL-2) and interferon-{gamma} production in phytohemagglutinin-activated whole blood were measured at 0 and 2 h postdose. The areas under the curves, cmin, cmax, and concentration at 2 h (c2 h) were also measured.

Results: We found no differences in CNA between groups receiving CNIs alone or combined with MMF [median (25th–75th percentiles)]: CsA2 h, 3.87 (3.00–6.85)% alkaline phosphatase (AP); CsA+MMF2 h, 3.90 (1.78–5.19)% AP; TRL2 h, 5.68 (3.02–16.00)% AP; TRL+MMF2 h, 11.80 (4.05–14.63)% AP. In vitro IL-2 production was significantly lower in the groups receiving combined therapy than in groups receiving CNIs alone [median (25th–75th percentiles)]: CsA2 h, 276.52 (190.41–385.25) ng/L; CsA+MMF2 h, 166.48 (81.06–377.01) ng/L (P <0.001); TRL2 h, 249.34 (127.48–363.50) ng/L; TRL+ MMF2 h, 122.13 (51.02–180.00) ng/L (P <0.001). The correlations (r) between c2 h and CNA 2 h postdose were as follows: CsA, r = -0.74; CsA+MMF, r = -0.84; TRL, r = -0.70; TRL+ MMF, r = -0.70 (P <0.001 in all cases).

Conclusions: The measurement of CNA may be of help in following the effect on the immune system of CNI treatments, even in combined therapies, but does not reflect the additional effect of MMF. In contrast, IL-2 in vitro production reflects the effect of both MMF and CNIs.






HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Copyright © 2003 by the American Association for Clinical Chemistry.