Longitudinal evaluation of mycophenolic acid pharmacokinetics in pediatric kidney transplant recipients. The role of post-transplant clinical and therapeutic variables.
This longitudinal study assessed the influence of post-transplant clinical and therapeutic variables in 50 kidney transplant recipients aged 2-19 yr receiving a triple immunosuppressive regimen consisting of cyclosporine microemulsion (CsA), steroids and MMF (300-400 mg/m(2) body surface area twice daily), the full pharmacokinetic profile (10 points) of which was investigated on post-transplant days 6, 30, 180 and 360. Total plasma MPA was measured by Enzyme Multiplied Immunoassay Technique. CsA therapeutic drug monitoring (TDM) was performed via C2 blood monitoring, while MPA TDM via C0. MPA Cmax, tmax, AUC0-12 and AUC0-4 pharmacokinetic profile changed significantly during the first post-transplant year. C0 was a poor predictor of the total MPA exposure [as measured by the area under the concentration-time curve AUC)], while a truncated AUC was a good surrogate of the 12-h profile (r = 0.91; p < 0.001) Graft function and cyclosporine therapy influenced MPA pharmacokinetics, as shown by the univariate and multivariate analyses. We conclude that because after transplantation MPA exposure varied over time, a strict TDM is advisable in the pediatric population.
Ghio
Luciana
L
Pediatric Nephrology Unit, Maggiore Policlinico Hospital, Mangiagalli and Regina Elena Foundation, IRCCS, Milan, Italy.
Ferraresso
Mariano
M
Zacchello
Graziella
G
Murer
Luisa
L
Ginevri
Fabrizio
F
Belingheri
Mirco
M
Peruzzi
Licia
L
Zanon
Franco
F
Perfumo
Francesco
F
Berardinelli
Luisa
L
Tirelli
Silvia
S
Dello Strologo
Luca
L
Fontana
Iris
I
Valente
Umberto
U
Cardillo
Massimo
M
Edefonti
Alberto
A
D000293:Adolescent; D000305:Adrenal Cortex Hormones / Q000493:pharmacokinetics; D000328:Adult; D000903:Antibiotics, Antineoplastic / Q000493:pharmacokinetics*; D019540:Area Under Curve; D002648:Child; D002675:Child, Preschool; D016572:Cyclosporine / Q000493:pharmacokinetics; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000493:pharmacokinetics*; D016030:Kidney Transplantation; D008137:Longitudinal Studies; D008297:Male; D009173:Mycophenolic Acid / Q000031:analogs & derivatives / Q000493:pharmacokinetics*; D011184:Postoperative Period; D014018:Tissue Distribution; D055815:Young Adult
D000305:Adrenal Cortex Hormones; D000903:Antibiotics, Antineoplastic; D007166:Immunosuppressive Agents; D016572:Cyclosporine; D009173:Mycophenolic Acid