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Evolution of the absorption profile of cyclosporine A in renal transplant recipients: a longitudinal study of the de novo and maintenance phases.
Nephrol Dial Transplant 2006; 21(1):197-202ND

Abstract

BACKGROUND

Therapeutic drug monitoring for cyclosporine microemulsion (CsA-ME) is often performed using either trough levels (C0) or levels at 2 h post-dose (C2). This analysis assessed changes in C0 and C2 and their relationship to CsA-ME dose over time post-transplant in renal transplant patients.

METHODS

Data were obtained from MO2ART, a prospective multicentre trial in which CsA-ME dose was adjusted based on C2 level. All 98 patients in whom C0 and C2 were available at day 5, month 3 and month 12 were included, out of 234 who completed the 12 month study. Normalized dose (ND) of CsA-ME, defined as dose per kilogram body weight, was calculated, together with C0/ND, C2/ND and C2/C0.

RESULTS

C0/ND and C2/ND both increased between day 5 and month 3: C0/ND from 33+/-15 to 53+/-24 (ng/ml)/(mg/kg) and C2/ND from 161+/-64 to 248+/-80 (ng/ml)/(mg/kg). Between month 3 and month 12, C2/ND remained stable but C0/ND decreased to 42+/-20 (ng/ml)/(mg/kg) while the C2/C0 ratio increased from 5.2+/-1.9 to 6.5+/-2.3, indicating an acceleration of drug elimination. The inter-individual coefficient of variation was higher for C0/ND than for C2/ND at 3 months (45 vs 32%, P<0.05) and at 12 months (48 vs 31%, P<0.01).

CONCLUSIONS

CsA clearance accelerates between months 3 and 12 post-transplant, resulting in lower C0 levels for a given exposure (as measured by C2). As a consequence, C0 monitoring may progressively underestimate CsA exposure during the first year post-transplant. C2 monitoring contributes to improved individualized CsA-ME treatment in both the de novo phase and beyond month 3.

Authors+Show Affiliations

Department of Nephrology and Clinical Immunology, C.H.U. Tours, 2 Boulevard Tonnellé 37044 Tours, France, and Royal Prince Alfred Hospital, Sydney, Australia. buchler@med.univ-tours.frNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Comparative Study
Journal Article
Multicenter Study
Randomized Controlled Trial
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

16204301

Citation

Büchler, Matthias, et al. "Evolution of the Absorption Profile of Cyclosporine a in Renal Transplant Recipients: a Longitudinal Study of the De Novo and Maintenance Phases." Nephrology, Dialysis, Transplantation : Official Publication of the European Dialysis and Transplant Association - European Renal Association, vol. 21, no. 1, 2006, pp. 197-202.
Büchler M, Chadban S, Cole E, et al. Evolution of the absorption profile of cyclosporine A in renal transplant recipients: a longitudinal study of the de novo and maintenance phases. Nephrol Dial Transplant. 2006;21(1):197-202.
Büchler, M., Chadban, S., Cole, E., Midtvedt, K., Thervet, E., Prestele, H., & Keown, P. (2006). Evolution of the absorption profile of cyclosporine A in renal transplant recipients: a longitudinal study of the de novo and maintenance phases. Nephrology, Dialysis, Transplantation : Official Publication of the European Dialysis and Transplant Association - European Renal Association, 21(1), pp. 197-202.
Büchler M, et al. Evolution of the Absorption Profile of Cyclosporine a in Renal Transplant Recipients: a Longitudinal Study of the De Novo and Maintenance Phases. Nephrol Dial Transplant. 2006;21(1):197-202. PubMed PMID: 16204301.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Evolution of the absorption profile of cyclosporine A in renal transplant recipients: a longitudinal study of the de novo and maintenance phases. AU - Büchler,Matthias, AU - Chadban,Steve, AU - Cole,Edward, AU - Midtvedt,Karsten, AU - Thervet,Eric, AU - Prestele,Hans, AU - Keown,Paul, Y1 - 2005/10/04/ PY - 2005/10/6/pubmed PY - 2006/3/1/medline PY - 2005/10/6/entrez SP - 197 EP - 202 JF - Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association JO - Nephrol. Dial. Transplant. VL - 21 IS - 1 N2 - BACKGROUND: Therapeutic drug monitoring for cyclosporine microemulsion (CsA-ME) is often performed using either trough levels (C0) or levels at 2 h post-dose (C2). This analysis assessed changes in C0 and C2 and their relationship to CsA-ME dose over time post-transplant in renal transplant patients. METHODS: Data were obtained from MO2ART, a prospective multicentre trial in which CsA-ME dose was adjusted based on C2 level. All 98 patients in whom C0 and C2 were available at day 5, month 3 and month 12 were included, out of 234 who completed the 12 month study. Normalized dose (ND) of CsA-ME, defined as dose per kilogram body weight, was calculated, together with C0/ND, C2/ND and C2/C0. RESULTS: C0/ND and C2/ND both increased between day 5 and month 3: C0/ND from 33+/-15 to 53+/-24 (ng/ml)/(mg/kg) and C2/ND from 161+/-64 to 248+/-80 (ng/ml)/(mg/kg). Between month 3 and month 12, C2/ND remained stable but C0/ND decreased to 42+/-20 (ng/ml)/(mg/kg) while the C2/C0 ratio increased from 5.2+/-1.9 to 6.5+/-2.3, indicating an acceleration of drug elimination. The inter-individual coefficient of variation was higher for C0/ND than for C2/ND at 3 months (45 vs 32%, P<0.05) and at 12 months (48 vs 31%, P<0.01). CONCLUSIONS: CsA clearance accelerates between months 3 and 12 post-transplant, resulting in lower C0 levels for a given exposure (as measured by C2). As a consequence, C0 monitoring may progressively underestimate CsA exposure during the first year post-transplant. C2 monitoring contributes to improved individualized CsA-ME treatment in both the de novo phase and beyond month 3. SN - 0931-0509 UR - https://www.unboundmedicine.com/medline/citation/16204301/Evolution_of_the_absorption_profile_of_cyclosporine_A_in_renal_transplant_recipients:_a_longitudinal_study_of_the_de_novo_and_maintenance_phases_ L2 - https://academic.oup.com/ndt/article-lookup/doi/10.1093/ndt/gfi113 DB - PRIME DP - Unbound Medicine ER -