A six-hour extrapolated sampling strategy for monitoring mycophenolic acid in renal transplant patients in the Indian subcontinent

• Published in: Journal of postgraduate medicine (Bombay) Vol. 52; no. 4; pp. 248 - 252
• Main Author: Fleming DH, Mathew BS, John GT, Chandy SJ, Manivannan J, Jeyaseelan V
• Format: Journal Article
• Language: English
• Published: India Medknow Publications and Staff Society of Seth GS Medical College and KEM Hospital, Mumbai, India 01-10-2006; Medknow Publications and Media Pvt. Ltd; Medknow Publications & Media Pvt. Ltd
• Subjects: Adolescent; Adult; Area Under Curve; Dosage and administration; Drug Monitoring - methods; Drug utilization; Humans; Immunosuppressive Agents - blood; Immunosuppressive Agents - pharmacokinetics; India; Kidney Transplantation; Measurement; Methods; Middle Aged; Mycophenolate mofetil; Mycophenolic Acid - blood; Mycophenolic Acid - pharmacokinetics; Mycophenolic acid, therapeutic drug monitoring; Time Factors; India
• ISSN: 0022-3859; 0972-2823

Background : Therapeutic drug monitoring for mycophenolic acid (MPA) is
increasingly being advocated. Thepresent therapeutic range relates to
the 12-hour area under the serum concentration time profile
(AUC).However, this is a cumbersome, tedious, cost restricting
procedure. Is it possible to reduce this samplingperiod? Aim : To
compare the AUC from a reduced sampling strategy with the full 12-hour
profile for MPA. Settings and Design : Clinical Pharmacology Unit of a
tertiary care hospital in South India. Retrospective, paireddata.
Materials and Methods : Thirty-four 12-hour profiles from post-renal
transplant patients on Cellcept ® wereevaluated. Profiles were
grouped according to steroid and immunosuppressant co-medication and
the timeafter transplant. MPA was estimated by high performance liquid
chromatography with UV detection. From the12-hour profiles the AUC up
to only six hours was calculated by the trapezoidal rule and a
correction factorapplied. These two AUCs were then compared.
Statistical Analysis : Linear regression, intra-class correlations
(ICC) and a two-tailed paired t-test were appliedto the data. Results :
Comparing the 12-hour AUC with the paired 6-hour extrapolated AUC, the
ICC and linear regression(r2) were very good for all three groups. No
statistical difference was found by a two-tailed paired t-test. Nobias
was seen with a Bland Altman plot or by calculation. Conclusion : For
patients on Cellcept ® with prednisolone ± cyclosporine the
6-hour corrected is an accuratemeasure of the full 12-hour AUC.