Glipizide treatment of post-transplant diabetes does not interfere with cyclosporine pharmacokinetics in renal allograft recipients.
BACKGROUND
Glipizide is an oral antidiabetic drug that has been used in the treatment of post-transplant diabetes mellitus (PTDM). However, a published case report has indicated a possible interaction of glipizide with cyclosporine (CsA) pharmacokinetics in two renal transplant (tx) patients. The aim of this open prospective study was to investigate whether glipizide interacts with CsA pharmacokinetics in renal tx patients with PTDM.


METHODS
Eleven renal tx patients (29-74 years of age) with PTDM who received Sandimmun Neoral as part of their immunosuppressive therapy were investigated. No patients had suffered any significant rise in serum creatinine (20%) from any cause over the last 2 wk before the study. Mean S-creatinine was 137 mumol/L (87-220). The mean CsA dose and whole blood concentration remained unchanged during the study. CsA whole blood concentrations were monitored over 12 h in all patients in random order, both on and off glipizide treatment. Blood samples were drawn immediately before the morning dose of CsA was given (trough) and 0.5, 1, 1.5, 2, 3, 4, 6 and 12 h after administration.


RESULTS
Whole blood trough CsA concentration was not altered by glipizide treatment, 256 +/- 76 micrograms/L off and 242 +/- 73 micrograms/L (mean +/- SD) with glipizide coadministration. The area under the curve (AUC) and terminal half-life of CsA remained unchanged with glipizide treatment: 6391 +/- 1483 micrograms/L per h and 7.3 +/- 1.5 h without; and 6279 +/- 1601 micrograms/L per h and 7.1 +/- 1.8 h with glipizide, respectively. No change in the CsA peak concentration (Cmax) was observed: 1507 +/- 406 micrograms/L without and 1469 +/- 538 micrograms/L with glipizide coadministration.


CONCLUSIONS
CsA pharmacokinetics is not significantly altered by glipizide coadministration.
Sagedal
S
S
Department of Internal Medicine, National Hospital, Oslo, Norway.
Asberg
A
A
Hartmann
A
A
Bergan
S
S
Berg
K J
KJ
D000328:Adult; D000368:Aged; D016572:Cyclosporine / Q000493:pharmacokinetics* / Q000627:therapeutic use; D003920:Diabetes Mellitus / Q000188:drug therapy* / Q000209:etiology; D004347:Drug Interactions; D005260:Female; D005913:Glipizide / Q000494:pharmacology* / Q000627:therapeutic use; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D007166:Immunosuppressive Agents / Q000493:pharmacokinetics* / Q000627:therapeutic use; D016030:Kidney Transplantation / Q000009:adverse effects*; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies
D007004:Hypoglycemic Agents; D007166:Immunosuppressive Agents; D016572:Cyclosporine; D005913:Glipizide