Cyclosporine pharmacokinetics in normal and pancreatectomized dogs

Oral and i.v. cyclosporine (Cs) pharmacokinetics determined from radioimmunoassay (RIA) data were compared in normal and pancreatectomized dogs. An altered pharmacokinetics of Cs was observed in the pancreatectomized dogs that include: a 170% larger central compartment volume; a 34% greater total-body clearance; and lower steady-state average serum concentrations relative to the normals. Even though there were marked intersubject variations, both groups displayed a triexponential decline in Cs serum concentrations and disposition kinetics. Following 7 daily oral doses of commercial cyclosporine (CsA) (20 mg/kg) the Cs serum trough concentrations of the pancreatectomized dogs were consistently below 100 ng/ml, while those of the normal dogs were above 400 ng/ml. No alteration of CsA oral absorption was noted following pancreatectomy. This study suggests that frequent serum Cs concentration monitoring, with appropriate dosage adjustments, even in normals, is necessary to assure adequate drug levels. More significantly, the CsA dosage for pancreatectomized dogs should be several times greater to maintain serum concentrations comparable to normal dogs.