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Tacrolimus pharmacokinetics in BMT patients
G W Boswell1, I Bekersky, J Fay
1Experimental Therapeutics, Fujisawa USA, Inc, Deerfiled, IL 60015, USA.
Bone Marrow Transplantation
|March 5, 1998
Summary
Tacrolimus pharmacokinetics in bone marrow transplant patients were evaluated. Co-administration with other drugs did not alter tacrolimus levels, and trough concentrations reliably indicated drug exposure for monitoring.
Area of Science:
- Pharmacology
- Hematology
- Transplantation
Background:
- Tacrolimus is an immunosuppressant crucial for preventing graft-versus-host disease after bone marrow transplantation (BMT).
- Understanding tacrolimus pharmacokinetics is essential for optimizing therapeutic efficacy and minimizing toxicity in BMT recipients.
Purpose of the Study:
- To characterize the pharmacokinetics of tacrolimus in BMT patients.
- To assess the impact of co-administered corticosteroids and methotrexate on tacrolimus pharmacokinetics.
- To evaluate the utility of trough concentrations for therapeutic drug monitoring.
Main Methods:
- Noncompartmental pharmacokinetic analysis of whole blood tacrolimus concentrations after intravenous (IV) and oral (PO) administration.
- Patients received initial IV tacrolimus, followed by PO dosing, with concomitant IV methotrexate and corticosteroids.
- Correlation analysis between trough concentrations (Cmin) and area under the curve (AUC).
Main Results:
- Tacrolimus pharmacokinetics did not differ significantly between single and steady-state doses.
- Mean terminal elimination half-life was 18.2 h, total body clearance was 71 ml/h/kg, and volume of distribution was 1.67 L/kg.
- Oral bioavailability ranged from 31-49%. Co-administration of methylprednisolone or methotrexate did not alter tacrolimus pharmacokinetics.
- Trough tacrolimus blood concentrations at 0 h and 12 h strongly correlated with AUC(0-12), indicating their reliability for monitoring drug exposure.
Conclusions:
- Tacrolimus pharmacokinetics in BMT patients are well-defined.
- Concomitant use of corticosteroids and methotrexate does not significantly impact tacrolimus pharmacokinetics.
- Trough tacrolimus concentrations serve as a reliable indicator of drug exposure, facilitating effective therapeutic drug monitoring in BMT management.