Evaluación de interacción medicamentosa de voriconazol-ciclosporina en pacientes pediátricos que reciben trasplante de precursores hematopoyéticos (2013-2014) / Drug interaction of voriconazole-cyclosporine in children undergoing hematopoietic stem cell transplantation (2013-2014)

Background: Drug interactions (DI) in patients receiving hematopoietic stem cell transplantation (HSCT) are common and clinically significant, highlighting: anticonvulsants, voriconazole (VCZ) and cyclosporine (CsA), which require monitoring. Objective: To describe the interactions between CsA-VCZ in children undergoing HSCT. Methods: Retrospective, descriptive study in immunocompromised children hospitalized since January 2013 to December 2014 at Bone Marrow Transplant Unit, Hospital Dr. Luis Calvo Mackenna, who received CsA and VCZ. Results: The median age was 5 years (3-6) and the median weight was 20 kg (17-30). Sixtythree baseline drug levels were analyzed, of those, 27 were CsA drug levels obtained previous to using VCZ and 36 were CsA drug levels collected concomitantly with VCZ. In the group CsA previous to VCZ, the CsA dose was 4.6 ± 2.6 (mg/ kg/ day) and the CsA average level was 188.8 ± 84.1 (μg/ml). In the group of CsA concomitantly with VCZ, the dose of CsA was 5.5 ± 3.0 (mg/ kg/day) (p = 0.07) and CsA average level was significantly higher: 232.5 ± 106.7 (μg/ml) (p = 0.04). Conclusion: This study shows an increased level of CsA when it is used together with VCZ. Therapeutic drug monitoring could improve the management of the DI and optimize the co-administration of CsA and VCZ.

Introducción: Las interacciones medicamentosas (IM) en el trasplante de progenitores hematopoyéticos (TPH) son comunes y clínicamente significativas, especialmente en: anticonvulsivantes, voriconazol (VCZ) y ciclosporina (CsA). Objetivo: Describir las interacciones de CsA-VCZ en pacientes con TPH. Métodos: Estudio descriptivo, retrospectivo, en pacientes receptores de TPH entre enero de 2013 y diciembre de 2014 en la Unidad de Trasplante de Médula Ósea del Hospital Dr. Luis Calvo Mackenna, que recibieran CsA y VCZ. Resultados: Edad media: 5 años (3-6), peso promedio: 20 kg (17-30). Se analizaron 63 concentraciones plasmáticas de CsA, 27 eran concentraciones de CsA previas al uso de VCZ y 36 concentraciones plasmáticas de CsA concomitantes con VCZ. En el grupo de CsA previo a VCZ, la dosis de CsA fue 4,6 ± 2,6 (mg/kg/día) y la concentración media de CsA 188,8 ± 84,1 (μg/ml). En el grupo de CsA en forma concomitante con VCZ, la dosis de CsA fue de 5,5 ± 3,0 (mg/kg/día) (p 0,07) y la concentración media de CsA fue: 232,5 ± 106,7 (μg/ml) (p = 0,04). Conclusión: Se demostró un aumento de las concentraciones plasmáticas de CsA en IM con VCZ. La monitorización terapéutica podría mejorar el manejo de la IM y optimizar la coadministración de CsA y VCZ.

Pharmacokinetics of cyclosporin: a microemulsion in children with idiopathic nephrotic syndrome

OBJECTIVE: We present a prospective study of a microemulsion of cyclosporin to treat idiopathic nephrotic syndrome in ten children with normal renal function who presented cyclosporin trough levels between 50 and 150 ng/ml and achieved complete remission with cyclosporin. To compare the pharmacokinetic parameters of cyclosporin in idiopathic nephrotic syndrome during remission and relapse of the nephrotic state. METHOD: The pharmacokinetic profile of cyclosporin was evaluated with the 12-hour area under the timeconcentration curve (auc0-12) using seven time-point samples. This procedure was performed on each patient during remission and relapse with the same cyclosporin dose in mg/kg/day. The 12-hour area under the timeconcentration curve was calculated using the trapezoidal rule. All of the pharmacokinetic parameters and the resumed 4-hour area under the time-concentration curve were correlated with the 12-hour area under the timeconcentration curve. ClinicalTrials.gov:NCT01616446. RESULTS: There were no significant differences in any parameters of the pharmacokinetic of cyclosporin during remission and relapse, even when the data were normalized by dose. The best correlation with the 12-hour area under the time-concentration curve was the 4-hour area under the time-concentration curve on remission and relapse of the disease, followed by the 2-hour level after cyclosporin (c2) dosing in both disease states. CONCLUSIONS: These data indicate that the same parameters used for cyclosporin therapeutic monitoring estimated during the nephrotic state can also be used during remission. Larger controlled studies are needed to confirm these findings.

Influence of Lactate Dehydrogenase and Cyclosporine A Level on the Incidence of Acute Graft-versus-host Disease After Allogeneic Stem Cell Transplantation

Previous reports have suggested that a high serum cyclosporine A (CsA) level could result in a lower incidence of acute-graft-versus-host disease (aGVHD). An elevated serum lactate dehydrogenase (LDH) level has been reported to be an adverse predictor of outcome in stem cell transplantation (SCT) for acute myeloid leukemia. In this study, we retrospectively analyzed the records of 24 patients who received allogeneic SCT from an HLA-matched sibling donor for acute and chronic myelogenous leukemia. Univariate analysis showed that two factors (the serum CsA level at the third week after SCT and the LDH level at the third week after SCT) were significantly associated with the incidence of aGVHD among several variables (age, sex, stem cell source, cell dose, C-reactive protein, absolute lymphocyte count, conditioning regimens, and time to engraftment). A higher serum level of CsA and lower serum LDH level at the third week after SCT were associated with a lower incidence of aGVHD (P=0.015, 0.030). In multivariate analysis, the serum CsA level (hazard ratio [HR], 0.12; 95% confidence interval [CI], 0.022-0.652, P=0.0014) and serum LDH level (HR, 6.59; 95% CI, 1.197-36.316, P=0.030) at the third week after SCT were found to be independent factors that were significantly associated with the development of aGVHD. We conclude that a high CsA level and low LDH level might predict a low cumulative incidence of aGVHD after allogeneic transplantation from a matched sibling donor.

Homocysteine level in renal transplant recipients and its correlation to glomerular filtration rate, cyclosporine level and folate level

Cardiovascular disease [CVD] is the most common cause of death after renal transplantation [RT]. Hyperhomocysteinemia is identified as a risk factor for CVD. RT recipients [RTRs] have an excess prevalence of hyperhomocysteinemia. The objectives of this study were to determine homocysteine [tHCY] level in stable RTRs and correlate its level to graft function, cyslosporine level and folate level. Twenty RTRs of 1[st] living renal allografts, 16 males and 4 females with a mean age of 44.1 +/- 5.1 years and a transplant duration of 22.2 +/- 12.6 months were included in this study. Their mean serum creatinine, blood urea and GFR were 1.5 +/- 0.6 mg/dL, 63 +/- 27.7 mg/dL and 53.9 +/- 32.8 ml/ min respectively. Hyperhomocysteinemia was recorded in all RTRs, mild in 13 [65%] and moderate in 7 [35%] with a mean of 27.9 +/- 12.8 umol/L. Plasma folate level was low [4.5 +/- 5.5 ng/mL]. A significant positive correlation was recorded between tHCY level and both blood urea and serum creatinine [r 0.529, 0.279 respectively, P < 0.05]. There was a significant negative correlation between tHCY level and both GFR and plasma folate level [r - 0.375, - 0.416 respectively, P < 0.05]. No correlation between tHCY level and both duration of renal transplantation and cyclosporine level was recorded. In conclusion, inadequate folate level and or failure to restore normal renal function may be relevant to hyperhomocysteinemia observed in RTRs. tHCY level lowering can be achieved safely, rapidly and in-expensively with B-vitamin intervention

Relationship of cyclosporin and sirolimus blood concentrations regarding the incidence and severity of hyperlipidemia after kidney transplantation

The influence of drug concentrations on the development of persistent posttransplant hyperlipidemia was investigated in 82 patients who received cyclosporin A (CsA) and prednisone plus sirolimus (SRL) (52) or azathioprine (AZA) (30) during the first year after transplantation. Blood levels of CsA and SRL, daily doses of AZA and prednisone, and cholesterol, triglyceride, and glucose concentrations were determined during each visit (pretransplant and 30, 60, 90, 120, 180, and 360 days posttransplant). Persistent hyperlipidemia was defined as one-year average steady-state cholesterol (CavCHOL) or triglyceride (CavTG) concentrations above 240 and 200 mg/dL, respectively. Mean cholesterol and triglyceride concentrations increased after transplantation (P < 0.01) and were higher in patients receiving SRL compared to AZA (P < 0.001). Patients receiving SRL showed a significantly higher number of cholesterol (>229 or >274 mg/dL) and triglyceride (>198 or >282 mg/dL) determinations in the upper interquartile ranges. CsA and SRL interquartile ranges correlated with cholesterol concentrations (P = 0.001) whereas only SRL interquartile ranges correlated with triglyceride concentrations (P < 0.0001). Only pretransplant cholesterol concentration >205 mg/dL was independently associated with development of persistent hypercholesterolemia (CavCHOL >240 mg/dL, relative risk (RR) = 20, CI 3.8-104.6, P = 0.0004) whereas pretransplant triglyceride concentration >150 mg/dL (RR = 7.2, CI 1.6-32.4, P = 0.01) or >211 mg/dL (RR = 19.8, CI 3.6-107.9, P = 0.0006) and use of SRL (RR = 3, CI 1.0-8.8, P = 0.0049) were independently associated with development of persistent hypertriglyceridemia (CavTG >200 mg/dL). Persistent hypercholesterolemia was more frequent among patients with higher pretransplant cholesterol concentrations and was dependent on both CsA and SRL concentrations. Persistent hypertriglyceridemia was more frequent among patients with higher pretransplant triglyceride concentrations and was dependent on SRL concentrations.

Hipertrofia gengival em transplantados renais / Cyclosporine induced gingival hyperplasia in kidney transplants

OBJETIVO: Avaliar os fatores associados ao crescimento gengival excessivo em transplantados renais. MÉTODOS: A pesquisa foi realizada no Hospital Cajuru de Curitiba, no período de abril a outubro de 2002, com a participacão de 60 transplantados renais, em uso diário de ciclosporina e com pelo menos um segmento dentário. O protocolo de ensaio foi observacional transversal. O exame odontológico dos indivíduos consistiu da avaliacão dos segmentos dentários com verificacão do grau de crescimento da gengiva e do índice de placa bacteriana. Todos os participantes preencheram questionário com dados relacionados ao transplante renal, realizaram coleta de material para controle do nível sérico de ciclosporina e foram avaliados quanto ao peso e altura. Na comparacão dos resultados de amostras categóricas, utilizou-se o teste do Qui-quadrado e a correlacão de classes de Spearman. O teste t foi aplicado na comparacão das variáveis contínuas. RESULTADOS: Em pacientes tratados somente com ciclosporina, 47,2 por cento não apresentavam alteracões da gengiva, enquanto 52,8 por cento cursaram com crescimento gengival, sendo 30,6 por cento com grau > 2. Nos pacientes tratados com ciclosporina e nifedipina, notou-se que 29,2 por cento tinham gengiva normal e 70,8 por cento apresentaram crescimento gengival, sendo que em 45,8 por cento o comprometimento foi grau > 2. Não foi observada diferenca significativa dos resultados entre os gêneros masculino e feminino. Foi encontrada correlacão positiva entre o índice de placa bacteriana e o volume gengival (r = 0,3295; p<0,01). CONCLUSAO: Em transplantados renais, a hipertrofia gengival está associada ao uso de ciclosporina, isoladamente ou em concomitância com bloqueadores de cálcio, e apresenta uma correlacão com o índice de placa bacteriana.

[ relationship between the plasma level of cyclosporine-A and drug dose in patients of Kermanshah Kidney Transplantation Center]

Nowadays the main problem in transplantation is the complexity of host immune system protection against the immunological and destructive reactions of the transplanted organ. High serum level of the immunosuppressive drug may cause toxicity and low serum level leads to the rejection of the transplanted organ. Cyclosporine has been known as the most effective immunosuppressive drug. Our goal in this study was to determine the relationship between cyclosporine serum level and administered dose in renal transplant recipients in order to find the optimum cyclosporine dose in Kermanshah kidney transplantation center. This descriptive-analytical study with simple sampling was done on 80 renal transplant recipients [51 males and 29 females] in Kermanshah transplantation center. At least 6 months after transplantation, in patients with stable conditions, cyclosporine peak and trough levels were measured by specific monoclonal, Radio Immuno Assay [RIA] method over a period of 3 months. Other biochemical parameters were measured too. Data were analyzed by 2 and ANOVA tests. Mean cyclosporine Trough and Peak levels were 271.9 +/- 85.2 and 904.5 +/- 414.2 ng/ml respectively, for the treatment dose of 3.25 +/- 1.46 mg/kg B.W. There was no significant difference between trough and peak levels in all three administered doses and the range of administered dose was 1.79-4.71 mg/kg B.W. According to the findings, cyclosporine serum concentrations and the administered dose range differed from other studies. This may be due to pharmacologic and pharmacokinetic differences of the drug and individual physiological characteristics of patients. The minimum dose of 1.79 and maximum dose of 4.71 led to optimum treatment in stable patients and could prevent rejection or toxic effects. Cyclosporine peak level was obviously different from other studies; however it showed better relationship with clinical status. Conversion from the routine cyclosporine C[trough] monitoring to C[peak] monitoring is recommended in Kermanshah kidney transplantation center

Impact of tissue typing matching on early graft function

Our study was conducted in Nasser institute. 60 patients were included in the study. They -were on regular hemodialysis and underwent kidney transplantation [46 males and 14 females], with a mean age of [32.03 +/- 10.57] years. 17 cases had related living donors and 43 cases had unrelated living donors. Patients were followed for six months. There was non significant relationship [P>0.05] between Zero match, one mismatch out of 6, two mismatches out of 6 [of HLA-A, HLA-B and HLA-DR] and the survival of the graft. Also there was only significant difference between acutely rejected grafts and non-rejected grafts [P<0.05], with only one successful match out of 6, being having even more successful matches out of 6 but didn't have significant effect on survival of the graft. Having more than one halotype or less, in common between donor and recipient at tissue matching didn't differ much on outcome of the graft [P>0.05]- Being related or unrelated donors, gender of donors and recipients and blood grouping didn't affect much the outcome of the graft [P>0.05]. Cases with more than 1 successful match out of 6 had significant difference in serum creatinine between rejected and non rejected grafts

Reversible posterior leucoencephalopathy syndrome associated with bone marrow transplantation

Reversible posterior leucoencephalopathy syndrome (RPLS) has previously been described in patients who have renal insufficiency, eclampsia, hypertensive encephalopathy and patients receiving immunosuppressive therapy. The mechanism by which immunosuppressive agents can cause this syndrome is not clear, but it is probably related with cytotoxic effects of these agents on the vascular endothelium. We report eight patients who received cyclosporine A (CSA) after allogeneic bone marrow transplantation or as treatment for severe aplastic anemia (SSA) who developed posterior leucoencephalopathy. The most common signs and symptoms were seizures and headache. Neurological dysfunction occurred preceded by or concomitant with high blood pressure and some degree of acute renal failure in six patients. Computerized tomography studies showed low-density white matter lesions involving the posterior areas of cerebral hemispheres. Symptoms and neuroimaging abnormalities were reversible and improvement occurred in all patients when given lower doses of CSA or when the drug was withdrawn. RPLS may be considered an expression of CSA neurotoxicity

Comparison of the fluorescent polarization (TDx) and the enzymatic competitive (EMIT 2000) immune assays for the measurement of cyclosporin A blood concentration

Evaluation of Cyclosporin A (CyA) blood concentration is imperative in solid organ transplantation in order to achieve maximal immunosuppression with the least side effects. We compared the results of whole blood concentrations of CyA in 50 blood samples simultaneously evaluated by the fluorescent polarization immune assay (TDx) and the enzymatic competitive immune assay (EMIT 2000). There was a strong correlation between both kits for any range of CyA blood concentration (R=0.99, p<0.001). The within-run and between-days coefficient of variation were less than 4 percent for both assays. The cost for each CyA measurement was 50 percent lower for the EMIT assay when compared to the TDx assay. We concluded that the EMIT is as accurate as the TDx in measuring CyA blood concentration and has the advantage of a lower cost, as well as the possibility of widespread access to the EMIT methodology in contrast to the TDx equipment, allowing the laboratory to perform several routines within a working day

Gestaçäo pós transplante cardíaco. Relato de caso e revisäo / Pregnancy after cardiac transplantation. Report of one case and review

A 14-year-old female patient became pregnant 6 years after heart transplantation. The pregnancy evolved uneventfully, and the newborn infant was healthy. Five months after delivery, the mother was in good condition with preserved ventricular function, and the baby had normal neuro-psychomotor development. Even though the case reported here was a success, pregnancy following cardiac transplantation is considered a high-risk condition and remains contraindicated

Cyclosporine trough levels in renal graft recipients.

Blood Trough Levels (TL) of cyclosporine (CyA) [the drug panimun bioral cyclosporine oral solution USP--modified. Panacea Biotec Ltd], were monitored in 103 renal transplant patients who were receiving CyA orally. Two hundred and sixty-two blood concentrations of CyA were determined using a validated HPLC assay over a period of two years. Mean dose from week 1 until 2 years ranged from 7.65 +/- 0.9 to 2.73 +/- 0.8 mg/kg. Mean blood CyA levels ranged from 197.4 +/- 87.5 to 205.9 +/- 113.5. The TL concentration changes versus dose reduction were not markedly different after 2-4 weeks and remained within therapeutic range. Stabilised concentrations were achieved after first month. We conclude that the blood TL of CyA were in the nominal therapeutic range suitable for renal transplant patients.

Evaluation of kidney functions and cyclosporine levels in renal transplant patients on Panimum Bioral in post transplant period.

A retrospective analysis of the patients being given Panimun Bioral (microemulsion cyclosporine) after renal transplantation was done at IKRDC, (Institute of Kidney Diseases & Research Centre), Ahmedabad. A total of 21 patients were included for analysis. Patients were evaluated for various parameters e.g. weight, cyclosporine levels, S. Creatinine and BUN at three time schedules as 0 to > or = 30 days, > 30 to > or = 60 days and > 60 to 120 days after renal transplantation. The analysis of data obtained indicates the kidney function tests improved in these patients and therapeutically safe blood cyclosporine levels were achieved in all the three timeschedules.

Monitoramento dos níveis de ciclosporina em sangue total en transplantes renais / Measuring cyclosporine in whole blood in kidney transplantation176-8

Introduçao e Objetivos. Ciclosporina A é uma droga imunossupressora potente e efetiva no combate à rejeiçao de órgaos transplantados. No presente estudo, os autores avaliaram o emprego de um imunoensaio monoclonal com fluorescência polarizada (FPIAm), como um método alternativo ao radioimunoensaio (RIA) para determinaçao dos níveis de ciclosporina em sangue total. Material e Métodos. Amostras de sangue de 65 pacientes submetidos a transplante renal foram colhidas em frascos com EDTA 12 horas após a última dose de ciclosporina, via oral. Os níveis de cilcosporina foram avaliados por meio de radioimunoensaio com anticorpo monoclonal e imunoensaio monoclonal com fluorescência polarizada. Resultados e Conclusao. A análise estatística revelou um coeficiente de correlaçao entre os métodos de r = 0,9817 e o teste t de Student pareado mostrou haver diferença estatisticamente significante entre eles (p<0,05). A análise da regressao revelou que os métodos poderiam ser comparáveis por meio da equaçao Cya(FPIAm) = 1,06xCya(RIA) + 5,8, mostrando que FPIAm é um excelente método alternativo ao RIA, com as vantagens de ser rápido, de fácil execuçao, reprodutível e com resultados comparavéis aos obtidos por RIA.

Serotonin levels in plasma and platelets of cyclosporin a treated rats

Nephrotoxicity of cyclosporin A[CsA] is the major side effect of this potent immunosuppressive drug. In order to evaluate the involvement of serotonin in CsA nephrotoxicity, rats were treated with different doses [1,10,30 and 100 mg/kg/day] of CsA on four consecutive days. Elevated serum urea and creatinine levels was accompanied by structural evidence of varying degrees of cytoplasmic proximal tubular vacuolization. These biochemical and pathologic changes were accompanied by an elevation of serotonin level in plasma and the depletion of serotonin content of the platelets. It is suggested that the elevated plasma levels of serotonin in CsA treated rats may be the result of platelet activation and degranulation

Comparison of HPLC & EMIT methods of cyclosporine assay in blood after bone marrow transplantation.

Cyclosporine (CsA) analysis in blood from patients who had undergone bone marrow transplantation for various haematological disorders was done both by high performance liquid chromatography (HPLC) and enzyme multiplied immunoassay technique (EMIT) and the results were compared. HPLC kit from Biorad Laboratories, USA, and EMIT kit from SYVA, UK, were used. The procedure for EMIT was slightly modified in-house to suit the Hitachi 704 discrete selective analyser. The CsA values obtained by these two methods correlated well within the therapeutic range (r value 0.96), HPLC method being most suitable outside the therapeutic range. Although HPLC is the ideal method for CsA, EMIT is quite suitable and can be adopted by any laboratory with an autoanalyser incorporating our modified procedure.

Comparaçäo entre a dosagem de ciclosporina-A em amostras de sangue coletadas em papel de filtro e pela técnica habitual / Comparison between the dosage of cyclosporin-A in blood samples collected on filter paper and by the ordinary technique

A monitorizaçäo dos níveis sanguíneos da ciclosporina A (CsA) é fundamental para o uso racional deste medicamento. No Brasil, poucos laboratórios realizam dosagem de CsA, embora haja muitos centros de transplante. Desta forma, surgiu o problema de fazer chegar a amostra de sangue ao laboratório. A coleta de sangue em papel de filtro é técnica já empregada, em situaçöes especiais, há muito tempo. OBJETIVOS. Correlacionar a fidedignidade da dosagem de CsAem amostras de sangue coletadas em papel de filtro com as técnicas habituais de coleta. MÉTODOS. Foram estudados 20 pacientes transplantados com rim de cadáver em uso de CsA, associada à azatioprina e à prednisona. Noventa e cinco amostras de sangue foram coletadas em EDTA e subdivididas em duas alíquotas. Uma delas foi encaminhada, da forma habitual, para o laboratório clínico para dosagem sanguínea de CsA. Da outra alíquota foram pipetados 20 microlitros sobre papel de filtro que, após secagem, foram enviados, pelo correio, para outro laboratório, onde, após eluiçäo, foi feita a dosagem de CsA. Nos dois casos a técnica de dosagem foi a mesma, usando-se o radioimunoen-saio com anticorpo policlonal anti-CsA. RESULTADOS. A correlaçäo linear entre ambas as dosagens resultou r = 0,81, näo havendo diferença significativa. CONCLUSÖES. Este método se presta, portanto, para ser usado na prática clínica, o que, em país de dimensöes continentais como o Brasil, pode ser muito útil

Farmacocinética da ciclosporina e de seus metabólicos em pacientes submetidos a transplante renal / Pharmacokinetics of cyclosporine and its metabolites in patients undergoing kidney transplantation

A farmacocinética da ciclosporina demosntra grande variaçäo inter e intra-individual e profundas mudanças säo, freqüentemente, observadas após o transplante renal. OBJETIVO. analisar seriadamente a farmacocinética da ciclosporina e de seus metabólitos através da determinaçäo de sua concentraçäo sanguínea, em pacientes submetidos a transplante renal. MÉTODOS. Foram realizados 70 estudos em 29 pacientes, sendo 26 antes e 44 após o transplante renal. Em cada estudo a curva de absorçäo foi analisada mediante a determinaçäo da concentraçäo sanguínea da ciclosporina, utilizando radioimunoensaio com anticorpos monoclonais específicos (RIE-MoSP) e inespecíficos (RIE-MoNP), em 17 amostras colhidas após a sua administraçäo oral ou endovenosa (0; 0,5; 1; 2; 3; 4; 5; 6; 7; 8; 9; 10; 12; 16; 20; 23; 24h). Resultados. A área sob a curva da concentraçäo sanguínea de ciclosporina em funçäo do tempo (AUC), a biodisponibilidade (F), a concentraçäo máxima (Cmax) e as concentraçöes sanguíneas obtidas 12 e 24 horas após a sua administraçäo (C12 e C24), determinadas com RIE-MoSP, foram inferiores àquelas encontradas com RIE-MoNP, enquanto a depuraçäo (CL) e o volume de distribuiçäo (Vd) foram maiores. A meia-vida de eliminaçäo foi semelhante utilizando os dois métodos (t1/2). A absorçäo seguiu uma cinética de ordem zero, sendo observada uma correlaçäo inversa entre a dose de ciclosporina e a AUC/dose (r = 0,55, RIE-MoSP e r = 0,42, RIE-MoNP). A fraçäo de absorçäo (F) variou entre 18 por cento e 68 por cento (RIE-MoSP), sendo superestimada quando determinada com RIE-MoNP (38 por cento a 100 por cento), conseqüência da extensa metabolizaçäo na primeira passagem pelo intestino e fígado...

Otimizaçäo do uso da ciclosporina em transplante renal / Optimization of the use of cyclosporin in renal transplantation

Avaliamos retrospectivamente estratégias empregadas na otimizaçäo do uso clínico da ciclosporina (CSA) em transplante renal. Baseado na incidência de rejeiçäo aguda nos primeiros 15 dias do transplante, a administraçäo oral da CSA foi superior à infusäo endovenosa constante, apesar dos relatos divergentes na literatura. A falta de monitorizaçäo do nível sanguíneo da CSA e o uso de doses diferentes de esteróides podem ser responsáveis pelo encontro de tais resultados. A minitorizaçäo do nível sanguíneo de CSA foi útil no diagnóstico diferencial de rejeiçäo aguda (RA) e nefrotoxicidade por CSA (NTX), definindo faixas de concentraçäo sangüínea ideais onde o risco de desenvolvimento de algum tipo de disfunçäo foi menor. Esta "faixa terapêutica" ficou entre 200 e 400ng/mL, quando foi utilizado radioimunoensaio tricidado com anticorpo policlonal (PC-CSA-H3), e entre 100 e 250ng/mL, utilizando RIA com anticorpo monoclonal específico (ME-CSA-H3), observando-se uma correlaçäo com um r=0,82 entre os dois métodos em 122 determinaçöes simultâneas. Alteraçöes histológicas encontradas nas biópsias renais de pacientes com RA näo foram diferentes daquelas obtidas de pacientes com NTX, antes ou após 90 dias de transplante. Concluímos que, por näo dispormos, no momento, de um único método com elevada sensibilidade, especificidade e valor preditivo, a monitorizaçäo do nível sanguíneo de CSA associada à biópsia renal é a melhor forma de reduzir a incidência de disfunçäo do enxerto, assegurando uma maior sobrevida, a longo prazo