Effects of conversion from sirolimus oral solution to tablets in stable Taiwanese renal transplant recipients.
OBJECTIVE
Sirolimus (SRL) has a considerable inter- and intra- individual variability in clearance. Steady-state trough concentration (C(0)) is a reliable index of SRL exposure. This study assessed the effect of conversion of SRL oral solution to tablet form on C(0) in stable renal transplant recipients.


METHODS
Twenty two stable renal transplant recipients who had received calcineurin inhibitor (CNI)/SRL solution/ steroid for more than 3 months before conversion from SRL solution to tablets were included. C(0) values of SRL were compared for the periods of use of each dosage form. The relation between liver function and SRL levels was also assessed.


RESULTS
With a dose of 0.03 mg/kg/day, SRL solution and tablets achieved a similar dose-adjusted C(0) (mean +/- SEM, 2.9 +/- 0.3 ng/mL/mg) upon conversion. Similar results were found when multiple SRL C(0) values from different dosage form periods were compared. Four patients with persistent liver enzyme elevation had significantly higher dose-adjusted SRL C(0) values with both the solution (mean +/- SEM, 4.5 +/- 0.7 vs 2.3 +/- 0.1 ng/mL/mg; p < 0.01) and the tablet formulation (4.0 +/- 0.5 vs 2.6 +/- 0.2 ng/mL/mg; p < 0.05).


CONCLUSIONS
Conversion from SRL solution to SRL tablets did not significantly affect the dose-adjusted SRL C(0). The dose-adjusted C(0) of SRL in patients with persistent liver enzyme elevation was significantly higher than in those with normal liver function.
Wu
Fe-Lin Lin
FL
School of Pharmacy, College of Medicine, National Taiwan University, Taipei, Taiwan.
Tsai
Meng-Kun
MK
Sun
Shao-Wen
SW
Chen
Russel Rhei-Long
RR
Huang
Jin-Ding
JD
Lee
Po-Huang
PH
D000284:Administration, Oral; D000328:Adult; D019540:Area Under Curve; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage*; D016030:Kidney Transplantation; D008099:Liver / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D020123:Sirolimus / Q000008:administration & dosage* / Q000493:pharmacokinetics; D012996:Solutions; D013607:Tablets
D007166:Immunosuppressive Agents; D012996:Solutions; D013607:Tablets; D020123:Sirolimus