Laboratory Monitoring of Cyclosporine Pre-Dose Concentration (C 0) After Kidney Transplantation in Isfahan



Toloughamari Z^{1, 2} ; Palizban AA¹ Show Affiliations
Source: Iranian Journal of Medical Sciences Published:2003

Abstract

Background: Cyclosporine is the main immunosuppressive agent used in organ transplantation which leads to considerable improvement in graft survival. The large inter- and intra- patient variability in cyclosporine pharmacokinetics coupled with the agent's narrow therapeutic index and adverse effects necessitate therapeutic monitoring of cyclosporine blood levels. Objective: The aim of this study was to determine the extent of variability following oral administration of cyclosporine after kidney transplantation, and provide guidelines for administration of cyclosporine in Isfahan/Iran. Methods: The results of 2163 cyclosporine pre-dose blood samples obtained from 647 kidney transplant recipients (208 females, 439 males) with a median age of 34 years (range 11-54 years) were studied. Concentration of cyclosporine in the whole blood was determined by a radioimmunoassay using monoclonal antibodies specific for the drug. Statistical analyses were performed using SPSS. Results: The frequency distribution of C0 and daily oral dosage of cyclosporine exhibited wide interindividual variability. Cyclosporine oral dosage regimen ranged from 100 mg to 400 mg. Trough cyclosporine blood concentration (C 0) ranged from 18 ug/l to 1400 ug/l. The results of cyclosporine whole blood levels in 56% were always below the suggested therapeutic range (less than 200 ug/l) and in 14% of the samples seemed to be associated with the occurrence of toxic side effects. There were no significant differences in the median trough levels of kidney recipients according to gender (p = 0.36). Conclusion: For long-term management of kidney transplant recipients and in order to further optimize the use of cyclosporine, it is essential to standardize laboratory monitoring and clinical investigation of this agent.; Indications:Graft rejection prophylaxis in 647 patients who underwent kidney transplantation.; Patients:647 patients, age range 11-54 years (median 34 years), 208 females and 439 males.; TypeofStudy:A study determining the extent of inter-individual variability in Sandimmun predose concentrations (C0) as a method in therapeutic drug monitoring after kidney transplantation in Iran.; DosageDuration:3-11 mg/kg daily (median 7.9 mg/kg) orally in 2 divided doses. Duration not stated.; Results:The frequency distribution of C0 of Sandimmun exhibited wide interindividual variability. Trough C0 ranged from 18 mcg/l to 1400 mcg/l. Sandimmun trough blood levels in 56% of samples, were always (less than 200 mcg/I) below the suggested therapeutic range. In 30% of the samples, Sandimmun blood levels were more than 200 mcg/I and less than 400 mcg/I. In 12%, Sandimmun blood levels were more than 400 mcg/I and less than 800 mcg/I. In a total of 14%, levels of Sandimmun (C0>400 mcg/I) were associated with the occurrence of toxicities. Sandimmun blood levels correlated poorly with dose (p = 0.23). Analysis of trough concentrations by gender showed no significant difference (p = 0.36). The patients received varied doses. The mean dose was 298 mg daily (range: 100-700 mg). 45/647 (7%) of recipients received 100 mg of Sandimmun daily, 395/647 (61%) of recipients received 200-300 mg and 194/647 (30 %) received 300-475 mg of Sandimmun, which seemed to be lower than the recommended therapeutic dosage of this drug.; AdverseEffects:Unspecified number of patients experienced infectious episodes, nephrotoxicity, hepatotoxicity, and neurotoxicity.; AuthorsConclusions:For long-term management of kidney transplant recipients and in order to further optimize the use of cyclosporine, it is essential to standardize laboratory monitoring and clinical investigation of this agent.; FreeText:A total of 2163 blood samples were obtained from the patients. Sandimmun concentration in the whole blood was determined by radioimmunoassay using monoclonal antibodies.