Pharmacokinetics of cyclosporine shows high inter and intra-individual variability and changes in several parameters are often found after kidney transplantation. PURPOSE--Evaluate serial studies of the pharmacokinetics of cyclosporine and its metabolites in patients undergoing kidney transplantation. METHODS--The pharmacokinetics of cyclosporine and its metabolites were analyzed in 70 studies performed in 29 patients, 26 before and 44 after kidney transplantation. The blood cyclosporine concentration was determined in 17 samples obtained after is oral or intravenous administration, using radioimmunoassay with specific (RIE-MoSP) and nonspecific (RIE-MoNP) monoclonal antibodies. RESULTS--The values of area-under-the-time-concentration curve (AUC), bioavailability (F), peak concentration (Cmax) and the 12 and 24 trough levels (C12 and C24), determined with RIE-MoSP, were lower than that obtained with RIE-MoNP, and the clearance (CL) and the volume of distribution (Vd) were higher. The elimination half-lives (t1/2) for both methods were not different. The absorption followed a zero order kinetic, demonstrating an inverse correlation between cyclosporine dose (mg/kg) and AUC/dose (r = -0.55, RIE-MoSP and r = -0.42, RIE-MoNP). Bioavailability ranged between 18% and 68% (RIE-MoSP) and were overestimated when calculated using RIE-MoNP (38% to 100%) owing to extensive cyclosporine metabolization during the first passage through the intestine and the liver. The metabolic rate analyzed by the ratio of blood concentrations determined with RIE-MoNP and RIE-MoSP (NP/SP), increased during the first 12 hours after cyclosporine administration, and was higher after oral dosing. The hematocrit and the serum lipoproteins concentrations significantly correlated with several pharmacokinetics parameters, mainly when they were determined with RIE-MoSP. The correlation between one sample obtained at any time after cyclosporine administration and the AUC were unsatisfactory, even the trough levels of 12 and 24 hours. AUCs calculated with 3 selected samples chosen by multiple linear regression correlated with AUC calculated using 17 samples, with a determination coefficient higher than 0.95 (RIE-MoSP, r = 0.975; RIE-MoNP, r = 0.974). CONCLUSION--Among all the parameters calculated, parameters of total exposure to the drug (AUC, AUC/dose, Cssav) showed the best correlation with the dose of cyclosporine, hematocrit and serum lipoproteins concentration. The methodology simplification, reducing the number of samples to calculate AUC, could be a good strategy to apply routinely these parameters in clinical transplantation.

Adolescent↗

PubMedDate not supplied

[Correction of anemia in chronic kidney failure with lyophilized recombinant human erythropoietin using a subcutaneous approach].

The recombinant human erythropoietin (rHuEPO) by subcutaneous route has been considered the drug of choice for the correction of the anemia of chronic renal patients. PURPOSE--To evaluate the efficacy of a new preparation of rHuEPO in the correction of the anemia of chronic renal patients maintained by haemodialysis, exclusively administered by subcutaneous route, studying the adverse effects and searching for predictive factors for the response to this medication. METHODS--Twelve patients in regular haemodialysis were treated with freeze-dried rHuEPO by subcutaneous route during 18 months with initial doses of 20U/kg/dialysis. They were submitted to a careful clinical and laboratory monitoring for all this study. RESULTS--Eleven patients ended the study reaching the target hematocrit (Htc) of 30% and keeping it during the whole period of the study. The mean correction and maintenance doses of rHuEPO were 65U/kg/dialysis and 51U/kg/dialysis respectively. At the 12th week of the study a significative increase of Htc (18.4 +/- 3.5% vs. 25.4% +/- 3.8%, p < 0.05) was demonstrated. An increase of the erythrocytes and hemoglobin was concomitantly observed. Leucocytes and platelets increased significantly from the 24th week and kept steadily until the end of study. Just potassium increased in the biochemistry analysis of the patients at the 4th and the 12th week of the study returning to the basal values at the 24th week. The evolution of the iron metabolism parameters demonstrated an intermitent and statistically significant decrease of transferrin saturation at the 1st, 12th and 24th week, returning to the basal levels at the end of study. The serum ferritin did not change (582.7 +/- 700, 9ng/mL vs. 700.0 +/- 651, 6ng/nL). The weight and the blood pressure did not change either, although 2 normotensive patients became hypertensive and 2 others with controlled hypertension needed drug rearrange for blood pressure control (36%). A patient had a seizure episode with a full recovery. CONCLUSION--The rHuEPO has proved to be a safe and an efficient drug with easily controlled adverse effect.

Adult↗

PubMedDate not supplied

[Medical propedeutics teaching].

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Education, Medical↗

PubMedDate not supplied

[Access to chronic dialysis treatment: deficient and unequal].

OBJECTIVE: To determine the fraction of patients with end-stage renal disease (ESRD) who received dialysis treatment in the city of São Paulo in 1991 and to investigate the influence of age in the access to dialysis. MATERIAL AND METHODS: All patients who received dialysis for ESRD in the city of São Paulo during 1991, and were registered in the Secretary of Health of São Paulo files were included in the study. In the same year, information was also collected on individuals who died having as basic cause of death a disease related to chronic renal failure. These data were obtained from death certificates files. Using simultaneously information from both data bases it was possible to ascertain the patients who died without receiving dialysis and to calculate the treated fraction in several age groups. RESULTS: Overall 25.6% of ESRD patients did not receive treatment. There was a progressive reduction in the fraction of patients treated for those older than 40 years. In children less or equal to 9 years of age the percentage of treatment was also reduced (29%). Individuals in the age groups 60-69 and 70-79 years had a chance about 5 and 11 times greater, respectively, of dying without receiving dialysis than those in the 20-29 years group. CONCLUSIONS: We estimate that at least one fourth of the ESRD patients died in São Paulo in 1991 without receiving dialysis treatment. Age is a major factor of discrimination for acceptance in chronic dialysis programs.

Adolescent↗

PubMedDate not supplied

Effect of the antiglucocorticoid RU-486 on glomerular hemodynamics in remnant nephrons.

Endogenous glucocorticoid (GC) has been proposed to play a role in the adaptive functions of remnant nephron and participates in the progression of renal disease. The effect of GC blockade by RU-486 (20 mg/kg), an anti-GC agent, on the progression of chronic renal failure (CRF) was evaluated in Munich-Wistar rats. CRF was induced by 5/6 nephrectomy. Global renal function, glomerular hemodynamics, proteinuria and renal histopathology studies were performed after 60 days of CRF induction. RU administration in control or CRF groups did not induce significant changes in total renal function, mean arterial or intraglomerular hydraulic pressures, 24-hour proteinuria or sclerosis index. However, RU induced a significant reduction in single-nephron glomerular filtration rate in the superficial nephrons in both groups' control (decreases 20%) and CRF (decreases 57%), without changing total glomerular filtration rate, when compared with vehicle administration. These reductions were due to a decline in glomerular plasma flow rate (QA) and in glomerular ultrafiltration coefficient (Kf). These data suggest that GC played a role in the adaptive hyperfiltration associated with the compensatory mechanism but did not participate in the genesis of proteinuria or glomerulosclerosis in this experimental model.

Animals↗