Abstract
The authors evaluated the intraindividual and interindividual variations in the pharmacokinetics of mycophenolic acid after oral administration of mycophenolate mofetil in 10 liver transplant patients. Mycophenolic acid and its metabolite, mycophenolic acid glucuronide, were measured in plasma and urine by high-pressure liquid chromatography. The plasma protein binding of mycophenolic acid was determined by ultrafiltration. The maximum concentration of mycophenolic acid in plasma increased significantly (P ≤ .05) with time from 9.1 ± 7.2 μg/mL (<1 week) to 36.7 ± 15.6 μg/mL (1 month). The area under the plasma concentration versus time curve of mycophenolic acid also increased significantly with time, from 50.8 ± 42.1 μg•h/mL to 118.0 ± 57.6 μg•h/mL (P ≤.05). The plasma protein binding of mycophenolic acid increased from 92% to 98%, and the apparent oral clearance [CL/F] decreased from 32.9 ± 21.4 L/h during the first study period to 9.0 ± 4.4 L/h (P ≤ .05) during the third study period. The apparent intrinsic clearance of mycophenolic acid did not change significantly over time. The ratio of the area under the curve of mycophenolic acid glucluronide to mycophenolic acid in plasma decreased with time (25.5 ± 21.2 vs 8.0 ± 3.3) but did not reach statistical significance. The increased binding of mycophenolic acid to plasma proteins with time after transplantation appeared to contribute to the intraindividual variation, whereas differences in the ability of the liver to metabolize mycophenolic acid between patients appear to contribute to the large interindividual variation in the pharmacokinetics of mycophenolic acid. The observations in this study support the concept of measuring the unbound concentration of mycophenolic acid to optimize immunosuppressive drug therapy with mycophenolic acid.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 34-41 |
| Number of pages | 8 |
| Journal | Journal of Clinical Pharmacology |
| Volume | 45 |
| Issue number | 1 |
| DOIs | |
| State | Published - Jan 1 2005 |
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All Science Journal Classification (ASJC) codes
- Pharmacology
- Pharmacology (medical)
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Intraindividual and interindividual variations in the pharmacokinetics of mycophenolic acid in liver transplant patients. / Pisupati, Jaya; Jain, Ashok; Burckart, Gilbert; Hamad, Imad; Zuckerman, Sheila; Fung, John; Venkataramanan, Raman.
In: Journal of Clinical Pharmacology, Vol. 45, No. 1, 01.01.2005, p. 34-41.Research output: Contribution to journal › Article
TY - JOUR
T1 - Intraindividual and interindividual variations in the pharmacokinetics of mycophenolic acid in liver transplant patients
AU - Pisupati, Jaya
AU - Jain, Ashok
AU - Burckart, Gilbert
AU - Hamad, Imad
AU - Zuckerman, Sheila
AU - Fung, John
AU - Venkataramanan, Raman
PY - 2005/1/1
Y1 - 2005/1/1
N2 - The authors evaluated the intraindividual and interindividual variations in the pharmacokinetics of mycophenolic acid after oral administration of mycophenolate mofetil in 10 liver transplant patients. Mycophenolic acid and its metabolite, mycophenolic acid glucuronide, were measured in plasma and urine by high-pressure liquid chromatography. The plasma protein binding of mycophenolic acid was determined by ultrafiltration. The maximum concentration of mycophenolic acid in plasma increased significantly (P ≤ .05) with time from 9.1 ± 7.2 μg/mL (<1 week) to 36.7 ± 15.6 μg/mL (1 month). The area under the plasma concentration versus time curve of mycophenolic acid also increased significantly with time, from 50.8 ± 42.1 μg•h/mL to 118.0 ± 57.6 μg•h/mL (P ≤.05). The plasma protein binding of mycophenolic acid increased from 92% to 98%, and the apparent oral clearance [CL/F] decreased from 32.9 ± 21.4 L/h during the first study period to 9.0 ± 4.4 L/h (P ≤ .05) during the third study period. The apparent intrinsic clearance of mycophenolic acid did not change significantly over time. The ratio of the area under the curve of mycophenolic acid glucluronide to mycophenolic acid in plasma decreased with time (25.5 ± 21.2 vs 8.0 ± 3.3) but did not reach statistical significance. The increased binding of mycophenolic acid to plasma proteins with time after transplantation appeared to contribute to the intraindividual variation, whereas differences in the ability of the liver to metabolize mycophenolic acid between patients appear to contribute to the large interindividual variation in the pharmacokinetics of mycophenolic acid. The observations in this study support the concept of measuring the unbound concentration of mycophenolic acid to optimize immunosuppressive drug therapy with mycophenolic acid.
AB - The authors evaluated the intraindividual and interindividual variations in the pharmacokinetics of mycophenolic acid after oral administration of mycophenolate mofetil in 10 liver transplant patients. Mycophenolic acid and its metabolite, mycophenolic acid glucuronide, were measured in plasma and urine by high-pressure liquid chromatography. The plasma protein binding of mycophenolic acid was determined by ultrafiltration. The maximum concentration of mycophenolic acid in plasma increased significantly (P ≤ .05) with time from 9.1 ± 7.2 μg/mL (<1 week) to 36.7 ± 15.6 μg/mL (1 month). The area under the plasma concentration versus time curve of mycophenolic acid also increased significantly with time, from 50.8 ± 42.1 μg•h/mL to 118.0 ± 57.6 μg•h/mL (P ≤.05). The plasma protein binding of mycophenolic acid increased from 92% to 98%, and the apparent oral clearance [CL/F] decreased from 32.9 ± 21.4 L/h during the first study period to 9.0 ± 4.4 L/h (P ≤ .05) during the third study period. The apparent intrinsic clearance of mycophenolic acid did not change significantly over time. The ratio of the area under the curve of mycophenolic acid glucluronide to mycophenolic acid in plasma decreased with time (25.5 ± 21.2 vs 8.0 ± 3.3) but did not reach statistical significance. The increased binding of mycophenolic acid to plasma proteins with time after transplantation appeared to contribute to the intraindividual variation, whereas differences in the ability of the liver to metabolize mycophenolic acid between patients appear to contribute to the large interindividual variation in the pharmacokinetics of mycophenolic acid. The observations in this study support the concept of measuring the unbound concentration of mycophenolic acid to optimize immunosuppressive drug therapy with mycophenolic acid.
UR - http://www.scopus.com/inward/record.url?scp=16644381286&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=16644381286&partnerID=8YFLogxK
U2 - 10.1177/0091270004270145
DO - 10.1177/0091270004270145
M3 - Article
C2 - 15601803
AN - SCOPUS:16644381286
VL - 45
SP - 34
EP - 41
JO - Journal of Clinical Pharmacology
JF - Journal of Clinical Pharmacology
SN - 0091-2700
IS - 1
ER -