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  • 1
    Electronic Resource
    Electronic Resource
    On the intraindividual variability and chronobiology of cyclosporine pharmacokinetics in renal transplantation (1993)
    Springer
    European journal of clinical pharmacology 44 (1993), S. 265-269 
    Details
    ISSN: 1432-1041
    Keywords: Cyclosporine ; Renal transplantation ; pharmacokinetics ; intraindividual variation ; circadian variation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The intraindividual variability and circadian variation of oral cyclosporine (CsA) pharmacokinetics were studied over 24 h in 18 renal transplant recipients at steady state, and in 10 of the patients during a second 24 h period. The absolute percentage intraindividual difference in daytime AUC (0–12 h) ranged from 2% to 54% (mean 30%), and the corresponding variability in nighttime AUC (0–12 h) ranged from 5% to 80% (mean 34%). The pharmacokinetic variables t1/2, tmax and Cmax were more variable than the AUC (0–12 h) both during the day and at night. The evening trough level was significantly lower than the morning trough level; 185 ng · ml−1 versus 223 ng · ml−1. This, together with a significantly longer t1/2 in the night than the day, suggested circadian variability in the pharmacokinetics of CsA. In a separate retrospective study in 162 renal transplant recipients given CsA by constant intravenous infusion, repeated CsA blood concentration measurements at steady state showed lower concentrations during the day than the night, suggesting higher CsA clearance during daytime. It is concluded that CsA pharmacokinetics in renal transplant recipients, besides the well-known interindividual variability, also displays large intraindividual variability as well as circadian variation. Our findings further emphasize the necessity and difficulty of pharmacological monitoring in the clinical use of CsA in organ transplantation.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00271369
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  • 2
    Electronic Resource
    Electronic Resource
    Pharmacokinetics of 15-deoxyspergualin studied in renal transplant patients receiving the drug during graft rejection (1994)
    Springer
    Transplant international 7 (1994), S. 5-10 
    Details
    ISSN: 1432-2277
    Keywords: 15-Deoxyspergualin, renal transplantation ; Renal transplantation, 15-deoxyspergualin Immunosuppression, 15-deoxyspergualin ; Rejection, 15-deoxyspergualin, renal transplantation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The pharmacokinetics of the novel immunosuppressant 15-deoxyspergualin (DSG) were studied in five renal transplant patients who participated in a dose-finding study for the treatment of renal graft rejection. DSG, in a dose of 4 or 6 mg/kg per day, was given in a 3-h i.v. infusion for 5 days, in combination with a 4-day course of i.v. methylprednisolone. Analyses of DSG in plasma and urine were performed by highperformance liquid chromatography (HPLC). Plasma samples were taken up to 12 h following infusion on treatment day 2 and again on day 4 or 5. Urine was collected during the infusion and up to 12 h following the infusion. DSG was rapidly eliminated from the plasma in an apparently biexponential manner. The mean t1/2alpha was 0.5 h (range 0.1–1.1 h) and the mean t1/2 beta 2.4 h (range 1.0–5.9 h). The mean Cmax was 4117 ng/ml (range 1944–7166 ng/ml) and the mean AUC 12505 ng·ml-1·h (range 5642–24435 ng·ml-1·h). Clerance ranged from 375 to 945 ml/min (mean 653 ml/min) and volume of distribution ranged from 0,2 to 1,4 l/kg (mean 0,7 l/kg). A small fraction (mean 1.6%, range 0.1%–2.7%) of the DSG dose given was excreted unmetabolized in the urine. The amount of DSG in the urine correlated strongly to renal function (P=0.0019). Pharmacokinetics were otherwise not affected by the degree of renal function. There were no significant differences in the pharmacokinetic determinants and no accumulation of the drug on study day 4 or 5, as compared to day 2. Therefore, the drug can safely be given to patients with impaired renal function. DSG did not affect cyclosporin pharmacokinetics.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00335656
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  • 3
    Electronic Resource
    Electronic Resource
    Rejection associated with early appearance of donor-reactive antibodies after kidney transplantation treated with plasmapheresis and administration of 15-deoxyspergualin (1992)
    Springer
    Transplant international 5 (1992), S. 189-192 
    Details
    ISSN: 1432-2277
    Keywords: Kidney transplantation ; 15-Deoxyspergualin, in kidney transplantation ; Plasmapheresis, in kidney transplantation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract In two kidney transplant patients, one of whom had panel-reactive antibodies (PRA) before transplantation, a pretransplant negative donor-recipient crossmatch became positive within the 1st week after transplantation. Simultaneously, good graft function deteriorated to a state of anuria. One patient graft biopsy showed a vascular rejection, whilst the other patient biopsy was unrevealing. Both patients were treated with plasmapheresis and a new immunosuppressive drug, 15-deoxyspergualin (DSG). Plasmapheresis was performed for 6 and 9 days, respectively, and DSG was given for 5 days in a dosage of 6 mg/kg body weight per day. One of the patients received methylprednisolone i.v. in addition. During treatment the crossmatch became negative and has since remained that way. In both patients the graft function was restored. No adverse effects were seen from the treatment, except for a slight leukocytopenia and thrombocytopenia.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00336067
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    Paper (German National Licenses)
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