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INTRA‐ AND INTERINDIVIDUAL VARIATION IN THE PHARMACOKINETICS OF TACROLIMUS (FK506) IN KIDNEY TRANSPLANT RECIPIENTS—IMPORTANCE OF TROUGH LEVEL AS A PRACTICAL INDICATOR
Author(s) -
Ihara Hideari,
Shinkuma Denji,
Ichikawa Yasuji,
Nojima Michio,
Nagano Shunsuke,
Ikoma Fumihiko
Publication year - 1995
Publication title -
international journal of urology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.172
H-Index - 67
eISSN - 1442-2042
pISSN - 0919-8172
DOI - 10.1111/j.1442-2042.1995.tb00444.x
Subject(s) - cmax , medicine , pharmacokinetics , tacrolimus , trough level , trough concentration , kidney transplantation , therapeutic drug monitoring , pharmacology , transplantation , urology , kidney transplant , concomitant , area under the curve
Background: Tacrolimus (FK506) is currently used as the primary immunosuppressant in clinical kidney transplantation in some centers. The purpose of this study was to evaluate the pharmacokinetics of this drug and to see if trough level, which has been used widely in therapeutic drug monitoring, can be used as an appropriate substitute for other pharmacokinetic measurement tests. Methods: The blood concentration‐time curve was studied in 10 kidney transplant recipients on 26 Occasions after oral dosage of 2 to 18 mg every 12 hours. Whole blood concentration was measured by two‐step irnmunoabsorption assay. Methylprednisolone was used as a concomitant immuno‐suppressive drug. Results: The blood concentration‐time curves showed remarkable interindividual variation. lntraindividual variation was also found, but the degree of variation was slight compared with interindividual variation. On 17 occasions of measurement in one patient, the dose was significantly correlated with trough (r = 0.684). C max (r = 0.838) and AUC 0–12 (r = 0.817). In nine patients on nine occasions, however, the dose was not significantly correlated with trough (r = 0.351), C max (r = 0.270) or AUC 0–12 (r = 0.355). t max ranged from one to four hours (mean + SD; 2.8 + 1.3) and fluctuated in both intra‐ and interindividual measurements. In spite of a wide variation in the blood concentration‐time‐curve patterns, a highly significant linear relationship between trough and C max or AUC 0–12 was observed in both intraindividual ( C max , r = 0.876; AUC 0–12 , r = 0.926) and interindividual ( C max , f = 0.943; AUC 0–12 , r = 984) measurements. Concluslons: We conclude that trough level is a practical acceptable indicator of the blood levels of tacrolimus, and can be used to monitor blood concentration.