Pharmacokinetic study of the new cyclosporine-A formulation (Neoral) in adult allogeneic bone marrow transplant recipients.
OBJECTIVE
A major problem encountered during oral cyclosporin-A (CsA) administration to prevent acute graft-versus-host-disease (GVHD) after allogeneic bone marrow transplantation (allo-BMT) is its irregular pharmacokinetics. The aim of this study was to evaluate the pharmacokinetics of Neoral, a new water-free microemulsion formulation of CsA.


METHODS
Eighteen patients aged over 18 were enrolled into the study. When able to eat normally after allo-BMT, patients received CsA orally and after 4 days a 12-hour CsA pharmacokinetic profile was constructed. Three patients received Sandimmune 10 mg/kg/day, 5 patients received Neoral 7.5 mg/kg/day and 10 patients Neoral 5 mg/kg/day. CsA concentration was analyzed on whole blood by high-performance liquid chromatography (HPLC).


RESULTS
Neoral showed concentration-time profiles characterized by a smooth and faster rise to the Cmax value compared to that produced by Sandimmune. The comparison between pharmacokinetic parameters obtained in patients receiving Neoral 5 mg/kg/day or 7.5 mg/kg/day showed a proportional increase of the AUC (4776+/-1084 vs. 7746+/-2006 ng/mL h) and C(max) (1027+/-203 vs. 1514+/-231 ng/mL). In all patients to whom 7.5 mg/kg/day of Neoral were given, C(trough) levels were always above the threshold of 200 ng/mL.


CONCLUSIONS
Our data suggest that oral administration of Neoral 7.5 mg/kg/day early after allo-BMT may represent an appropriate dose resulting in adequate CsA C(trough) levels without significant renal toxicity.
Divisione di Ematologia, Ospedali Riuniti di Bergamo, and Istituto di Ricerche Farmacologiche Mario Negri Bergamo, Italy.
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Dotti
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Gaspari
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Caruso
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Perico
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Remuzzi
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Barbui
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Rambaldi
D000328:Adult; D000368:Aged; D019540:Area Under Curve; D016026:Bone Marrow Transplantation; D016572:Cyclosporine / Q000493:pharmacokinetics*; D005260:Female; D006086:Graft vs Host Disease / Q000188:drug therapy / Q000517:prevention & control; D019337:Hematologic Neoplasms / Q000628:therapy; D006801:Humans; D007166:Immunosuppressive Agents / Q000493:pharmacokinetics*; D008297:Male; D008875:Middle Aged; D014184:Transplantation, Homologous
D007166:Immunosuppressive Agents; D016572:Cyclosporine