Pharmacokinetics and nephrotoxicity of cyclosporine.
Cyclosporine (CsA) is a potent immunosuppressive agent which has dramatically improved graft and patient survivals in clinical solid organ transplantation. However, CsA nephrotoxicity (NTX) is the most frequent and serious side effect of CsA therapy and occurs in a significant proportion of patients. The clinical presentation of NTX is that of reduced creatinine clearance, elevation of serum creatinine and a disproportionate rise in blood urea. The clinical picture occurs as three syndromes, namely acute, subacute and chronic CsA NTX. Regardless of the clinical syndrome, the pathoaetiology of NTX is related to decline in renal blood flow and increase in renal vascular resistance probably due to CsA induced changes in renal haemodynamics. Unfortunately, the dose that yields an optimal therapeutic index, namely maximal efficacy with minimal toxicity has yet to be defined. Optimal dosing is confounded by not only inter and intraindividual variabilities in drug absorption, distribution and metabolism, but also by the lack of a clear relationship between drug efficacy and trough CsA level monitoring. This paper describes the pharmacokinetics and nephrotoxicity of CsA and evaluates various strategies to overcome this toxicity.
Vathsala
A
A
Department of Renal Medicine, Singapore General Hospital.
Woo
K T
KT
Lim
C H
CH
D000042:Absorption; D016572:Cyclosporine / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000633:toxicity; D006801:Humans; D007165:Immunosuppression Therapy / Q000379:methods; D007668:Kidney / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D016030:Kidney Transplantation / Q000276:immunology
D016572:Cyclosporine