Effect of cyclosporin pharmacokinetics on renal allograft outcome in African-Americans.
African-Americans (A-As) experience inferior outcome after transplantation compared with other ethnic groups. Bioavailability of cyclosporin (CsA) has been implicated as a possible contributing factor. This paper describes the outcome of 32 A-A recipients of de novo renal allograft who received CsA-based triple immunotherapy according to individual pharmacokinetic profiles. Patients received CsA-microemulsion q 12 h, dosed initially at 3.5 mg/kg (8 am) and 3.0 mg/kg (8 pm). The am and pm doses were independently adjusted to achieve a 12-h area under the concentration-time curve (AUC0-12) of 6600-7200 nghr/mL and morning trough level (C0) of 250-325 ng/mL, respectively. Mean age was 43 +/- 12 yr, 37% (12) female. Mean AUC0-12 in 1 wk, 1, 3, 6, and 12 months were 7810 +/- 1880 nghr/mL, 9057 +/- 2097 nghr/mL, 7674 +/- 1912 nghr/mL, 7132 +/- 2040 nghr/mL, and 6503 +/- 1410 ngl/h with corresponding C0 of 301 +/- 79 ng/mL, 316 +/- 66 ng/mL, 275 +/- 59 ng/mL, 273 +/- 66 ng/mL, and 224 +/- 49 ng/mL, respectively. Acute rejection occurred in two patients (6%) 1 yr after transplantation. Prospective use of CsA pharmocokinetic profiles improves renal allograft outcome in A-As.
Emovon
Osemwegie E
OE
Department of Medicine, University of South Alabama, Mobile, AL, USA.
King
Judy A C
JA
Holt
Cindy Op't
CO
Singleton
Barbara
B
Howell
David
D
Browne
Barry J
BJ
D000328:Adult; D001741:Black or African American; D019540:Area Under Curve; D044383:Black People; D016572:Cyclosporine / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000627:therapeutic use; D004334:Drug Administration Schedule; D016903:Drug Monitoring; D004359:Drug Therapy, Combination; D005260:Female; D006084:Graft Rejection / Q000208:ethnology; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000627:therapeutic use; D016030:Kidney Transplantation / Q000208:ethnology*; D008297:Male; D009173:Mycophenolic Acid / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000627:therapeutic use; D011241:Prednisone / Q000008:administration & dosage / Q000627:therapeutic use
D007166:Immunosuppressive Agents; D016572:Cyclosporine; D009173:Mycophenolic Acid; D011241:Prednisone