PMID: 11903387Mar 21, 2002Paper

Diurnal cyclosporine dosing optimizes exposure and reduces the risk of acute rejection after kidney transplantation

Clinical Transplantation
B J BrowneO E Emovon

Abstract

Acute rejection (AR) following transplantation may be due to episodic subtherapeutic cyclosporine (CsA) levels related to diurnal variation of hepatic drug metabolism. We postulated that asymmetrical dosing of CsA based on individualized pharmacokinetic profiles would optimize drug exposure and decrease the risk of AR. We prospectively treated all patients undergoing kidney transplantation with a diurnally split dose of CsA microemulsion given q 12 hours (3.5 mg/kg q a.m., 3.0 mg/kg qPM). Morning doses were adjusted to reach a day-time area under the concentration curve (AUC) of 7,800 ng hour/ml (utilizing 2 hour and 6 hour levels) and evening doses were adjusted to a morning trough of 300 ng/ml. Patients received high-dose steroids tapered to 20 mg prednisone by day 6. CsA was started within 36 hours and mycophenolate mofetil (1000 mg q 12 hour) was added on day 3 in most patients and continued for 3 months. Only one patient received antibody induction. Thirty kidneys (67% cadaveric) were transplanted into 28 adult patients (50% African American, 57% men). Therapeutic targets were reached in all patients prior to discharge and maintained during the study period. At 3 months follow-up, there was not a single episode of document...Continue Reading

References

Jul 1, 1976·Agents and Actions·J F BorelH Stähelin
Dec 21, 1989·The New England Journal of Medicine·B D Kahan

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Citations

Sep 21, 2002·Lancet·Osemwegie E Emovon, Barry J Browne
Oct 10, 2002·Clinical Transplantation·Osemwegie E EmovonBarry J Browne
Jun 5, 2003·Clinical Transplantation·Osemwegie E EmovonBarry J Browne

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