RESUMO
OBJECTIVE: To evaluate lymphocyte reconstitution after protease inhibitor therapy in children with human immunodeficiency virus (HIV) infection. STUDY DESIGN: Forty-four HIV-infected children receiving ritonavir monotherapy followed by the addition of zidovudine and didanosine were evaluated during a phase I/II clinical trial. The cohort had a median age of 6.8 years and advanced disease (57% Centers for Disease Control and Prevention stage C, 73% immune stage 3) and was naive to protease inhibitor therapy. RESULTS: After 4 weeks of therapy, there was a significant increase in CD4(+) and CD8(+) T cells. CD4(+) T cells continued to increase, whereas CD8(+) T cells returned to baseline by 24 weeks. Unexpectedly, there was a significant increase in B cells. Changes in CD4(+) T-cell subsets revealed an initial increase in CD4(+) CD45RO T cells followed by a sustained increase in CD4(+) CD45RA T cells. Children <6 years of age had the highest increase in all lymphocyte populations. Significant improvement in CD4(+) T-cell counts was observed even in those children whose viral burden returned to pre-therapy levels. CONCLUSIONS: Early increases in lymphocytes after ritonavir therapy are a result of recirculation, as shown by increases in B cells and CD4(+) CD45RO and CD8(+) T cells. Children exhibited a high potential to reconstitute CD4(+) CD45RA T cells even with advanced disease and incomplete viral suppression.
Assuntos
Fármacos Anti-HIV/uso terapêutico , Infecções por HIV/tratamento farmacológico , Infecções por HIV/imunologia , Inibidores da Protease de HIV/uso terapêutico , Ritonavir/uso terapêutico , Adolescente , Relação CD4-CD8 , Linfócitos T CD4-Positivos , Linfócitos T CD8-Positivos , Criança , Pré-Escolar , Didanosina/uso terapêutico , Quimioterapia Combinada , Humanos , Imunofenotipagem , Lactente , Antígenos Comuns de Leucócito , Subpopulações de Linfócitos , Carga Viral , Zidovudina/uso terapêuticoRESUMO
BACKGROUND: Children with human immunodeficiency virus (HIV) infection have an increased susceptibility to severe and unusual infections, malignancies, and disorders characterized by abnormal lymphoproliferation (e.g., lymphoid interstitial pneumonitis). We report a novel disease entity associated with pediatric HIV infection that is characterized by massive enlargement of the thymus as a result of lymphoid hyperplasia and multicystic changes. METHODS: Eight patients with HIV infection and cystic enlargement of the thymus are subject of this report. The status of their HIV disease and its clinical and radiologic manifestations at the time of diagnosis of the mediastinal mass are described. Tissue specimens were obtained from six patients and examined by microscopy and immunohistochemistry. The specimens were also evaluated for the evidence of HIV and Epstein-Barr virus by in situ hybridization. RESULTS: Patients were between 2.1 and 12.1 years of age, with CD4+ cell counts between 102 and 733 cells/mm3. In all eight cases an anterior mediastinal mass was discovered incidentally on radiography of the chest, and computed tomography of the chest revealed a multicystic appearance. Histologic examination demonstrated distortion of the thymic architecture by focal cystic changes, lymphoid follicular hyperplasia, diffuse plasmacytosis, and multinucleated giant cells. In situ hybridization revealed HIV particles on the surface of follicular dendritic cells. Further, results of in situ hybridization for EBV were positive in lymphoid cells from biopsy samples of four patients. The patients were followed between 8 months and 4.8 years. In five patients the mass either decreased in size or resolved completely. CONCLUSIONS: We describe a series of children with HIV infection and multilocular thymic cysts. We hypothesize that aberrant immunoregulation in these HIV-infected children leads to follicular hyperplasia and multicystic changes in the thymus, causing massive enlargement. EBV infection might also contribute to the pathogenesis of this process. Because none of our patients had symptoms from the mass, and there was no evidence of malignancy in the examined biopsy samples, it seems prudent to manage such children with careful follow-up examinations.
Assuntos
Infecções Oportunistas Relacionadas com a AIDS/patologia , Cisto Mediastínico/patologia , Infecções Oportunistas Relacionadas com a AIDS/diagnóstico por imagem , Contagem de Linfócito CD4 , Criança , Pré-Escolar , DNA Viral/genética , Células Dendríticas/patologia , Células Dendríticas/virologia , Suscetibilidade a Doenças , Feminino , Seguimentos , Células Gigantes/patologia , HIV/genética , HIV/isolamento & purificação , Infecções por Herpesviridae/patologia , Herpesvirus Humano 4/genética , Herpesvirus Humano 4/isolamento & purificação , Humanos , Hiperplasia , Imuno-Histoquímica , Hibridização In Situ , Tecido Linfoide/diagnóstico por imagem , Tecido Linfoide/patologia , Tecido Linfoide/virologia , Transtornos Linfoproliferativos/patologia , Masculino , Cisto Mediastínico/diagnóstico por imagem , Cisto Mediastínico/virologia , Plasmócitos/patologia , Radiografia Torácica , Timo/diagnóstico por imagem , Timo/patologia , Timo/virologia , Tomografia Computadorizada por Raios X , Infecções Tumorais por Vírus/patologiaRESUMO
BACKGROUND: Lymph nodes serve as reservoirs for the replication of human immunodeficiency virus (HIV) type 1. Comparison of serial measurements of virus burden in lymph nodes and peripheral blood after a change in antiretroviral therapy may provide insights into pathogenic mechanisms and permit a more accurate assessment of a therapeutic response. STUDY DESIGN: Nevirapine was added to the drug regiment of eight children with HIV infection treated with the combination of zidovudine and didanosine who had increasing levels of serum p24 antigen. Lymph node biopsies were performed at entry and after 12 weeks of therapy. RESULTS: Neither CD4 counts nor p24 antigen level correlated with the degree of viremia as measured by ribonucleic acid copy numbers in plasma. Correlations were found between HIV DNA copy number in peripheral blood mononuclear cells and HIV DNA copy number in lymph nodes (p = 0.02), as well as between peripheral blood CD4 counts and lymph node architecture. The HIV signals in the lymph nodes conformed to the anatomic organization of apical light zones in the germinal centers; however, in more advanced disease stages, organized germinal centers disappeared as evidence by a decline in the extent of the follicular dendritic network. CONCLUSIONS: Lymph node biopsies in this small number of HIV-infected children revealed a progressive loss of an organized architecture, especially of the follicular dendritic network. This correlated with a progressive loss of CD4+ cells but not with other measures of disease stage, including viral load, as measured by ribonucleic acid copy numbers.
Assuntos
Infecções por HIV/virologia , HIV-1/isolamento & purificação , Linfonodos/virologia , Antivirais/uso terapêutico , Biópsia , Contagem de Linfócito CD4 , Criança , Pré-Escolar , DNA Viral/análise , Didanosina/administração & dosagem , Quimioterapia Combinada , Feminino , Proteína do Núcleo p24 do HIV/sangue , Infecções por HIV/tratamento farmacológico , Infecções por HIV/imunologia , Humanos , Hibridização In Situ , Lactente , Linfonodos/patologia , Masculino , Nevirapina , Piridinas/administração & dosagem , Viremia , Zidovudina/administração & dosagemRESUMO
OBJECTIVE: To study thyroid function in children infected with human immunodeficiency virus (HIV) and determine whether there are correlates of thyroid dysfunction with disease progression. STUDY DESIGN: Total and free thyroxine, triiodothyronine, reverse triiodothyronine, thyrotropin, and thyroxine binding globulin (TBG) were measured in 167 children with HIV infection (age, 1 to 19 years; mean, 9.15 years). SETTING: Pediatric Branch, National Cancer Institute. RESULTS: Free thyroxine was at or below the lower limit of normal (normal, 1.0 to 1.9 ng/dl) in 18% of the children; thyrotropin and TBG levels were above the normal range in 31% and 30%, respectively. There was an inverse correlation between CD4+ cell count and thyrotropin, and between CD4+ cell count and TBG. No correlation was found between thyroid function and other disease symptoms or medications. CONCLUSION: These findings indicate that thyroid abnormalities occur more frequently in children with HIV infection than was previously reported, have a different profile from the thyroid abnormalities associated with other chronic disease conditions, and correlate with disease progression.
Assuntos
Infecções por HIV/fisiopatologia , Glândula Tireoide/fisiopatologia , Hormônios Tireóideos/sangue , Adolescente , Análise de Variância , Contagem de Linfócito CD4 , Criança , Pré-Escolar , Progressão da Doença , Feminino , Infecções por HIV/sangue , Infecções por HIV/imunologia , Humanos , Masculino , Prevalência , Análise de RegressãoRESUMO
OBJECTIVES: Human immunodeficiency virus (HIV) infection in children can be complicated by the development of cardiac disease. Decreased left ventricular function has been temporally associated with the use of zidovudine (azidothymidine; AZT) in adults with HIV and has been associated with changes in cardiac muscle mitochondria in animal models. This study was done in an attempt to determine whether the cardiac disease is related to the antiretroviral therapy or to progressive HIV infection. METHODS: We retrospectively reviewed echocardiograms, clinical records, and laboratory data from 137 HIV-infected children who were being treated by the Pediatric Branch, National Cancer Institute, and who were receiving AZT or didanosine, both drugs, or no antiretroviral therapy. RESULTS: Despite correction of the echocardiographic results for HIV disease severity with markers such as CD4+ lymphocyte count, time since infection, mode of acquisition of HIV, and age, children who were treated with AZT had a lower average fractional shortening than those who were not treated with AZT (p < 0.00001). There was a nonlinear relation between days of AZT use and this There was a nonlinear relation between days of AZT use and this decrease in fractional shortening. The odds that a cardiomyopathy would develop was 8.4 times greater in children who had previously used AZT than in those who had never taken AZT (95% confidence interval, 1.7 to 42.0). Didanosine was not associated with the development of a cardiomyopathy. CONCLUSIONS: Treatment of HIV-infected children with AZT may be associated with the development of a cardiomyopathy; didanosine does not appear to increase the risk of cardiomyopathy. The continued use of AZT in a child in whom a cardiomyopathy develops should be carefully assessed, and all children receiving AZT should be followed by serial cardiac examination and echocardiograms.
Assuntos
Síndrome da Imunodeficiência Adquirida/tratamento farmacológico , Didanosina/farmacologia , Didanosina/uso terapêutico , HIV , Coração/efeitos dos fármacos , Zalcitabina/farmacologia , Zalcitabina/uso terapêutico , Zidovudina/farmacologia , Zidovudina/uso terapêutico , Contagem de Linfócito CD4 , Cardiomiopatias/diagnóstico , Cardiomiopatias/etiologia , Cardiomiopatias/fisiopatologia , Pré-Escolar , Relação Dose-Resposta a Droga , Ecocardiografia , Feminino , Coração/fisiopatologia , Humanos , Lactente , Recém-Nascido , Masculino , Prontuários Médicos , Estudos Retrospectivos , Índice de Gravidade de Doença , Zidovudina/efeitos adversosRESUMO
We report a case of disseminated intravascular coagulopathy, apparently caused by exposure to granulocyte colony-stimulating factor (G-CSF). The medical records of patients treated for more than 30 consecutive days with subcutaneously administered G-CSF were reviewed for the occurrence of thrombocytopenia or coagulation abnormalities. New-onset thrombocytopenia with a platelet count less than 100 x 10(9) cells/L (< 100,000 cells/mm3) developed in 9 of 23 patients (39%) after a median of 11 weeks of treatment with G-CSF at dosages between 1 and 10 micrograms/kg per day.
Assuntos
Coagulação Intravascular Disseminada/etiologia , Fator Estimulador de Colônias de Granulócitos/efeitos adversos , Infecções por HIV/terapia , Adolescente , Adulto , Antivirais/uso terapêutico , Fatores de Coagulação Sanguínea/efeitos dos fármacos , Criança , Pré-Escolar , Terapia Combinada , Coagulação Intravascular Disseminada/sangue , Feminino , Fator Estimulador de Colônias de Granulócitos/administração & dosagem , Hemofilia A/terapia , Humanos , Lactente , Injeções Subcutâneas , Contagem de Leucócitos , Masculino , Contagem de Plaquetas , Trombocitopenia/sangue , Trombocitopenia/etiologiaAssuntos
Síndromes de Imunodeficiência/epidemiologia , Neoplasias/epidemiologia , Síndrome da Imunodeficiência Adquirida/epidemiologia , Adulto , Fatores Etários , Doenças Autoimunes/epidemiologia , Criança , Pré-Escolar , Comorbidade , Humanos , Síndromes de Imunodeficiência/congênito , Incidência , Lactente , Estados UnidosRESUMO
As part of a phase I/II trial in children infected with human immunodeficiency virus, we studied the pharmacokinetics of zidovudine and didanosine administered as single agents and in combination. Zidovudine (60 to 180 mg/m2 per dose) was given orally every 6 hours, and didanosine (60 to 180 mg/m2 per dose) every 12 hours. Pharmacokinetic samples were obtained from 54 patients and the area under the plasma concentration-time curve (AUC) was estimated by means of a previously defined limited sampling strategy. Follow-up blood samples were obtained after 4 and 12 weeks of treatment. The mean AUC for zidovudine ranged from 4.8 mumol.hr per liter at 60 mg/m2 to 11.0 mumol.hr per liter at the 180 mg/m2 level, and increased in proportion to the dose. The mean AUC for didanosine ranged from 2.8 mumol.hr per liter (60 mg/m2) to 8.0 mumol.hr per liter (180 mg/m2), with a wide interpatient variability. The AUCs of zidovudine and didanosine remained unchanged when the agents were administered in combination. There was no significant change in the AUCs of either drug after 4 and 12 weeks in comparison with those on day 3 of therapy. However, there was greater interpatient and intrapatient variability with didanosine than with zidovudine. These observations have implications for the future utility of therapeutic drug monitoring with these agents.
Assuntos
Didanosina/farmacocinética , Infecções por HIV/tratamento farmacológico , Zidovudina/farmacocinética , Adolescente , Adulto , Criança , Pré-Escolar , Didanosina/administração & dosagem , Didanosina/uso terapêutico , Relação Dose-Resposta a Droga , Interações Medicamentosas , Monitoramento de Medicamentos , Quimioterapia Combinada , Feminino , Infecções por HIV/sangue , Humanos , Lactente , Masculino , Zidovudina/administração & dosagem , Zidovudina/uso terapêuticoRESUMO
OBJECTIVE: To determine the safety, tolerance, pharmacokinetics, and antimycobacterial activity of orally administered clarithromycin in children with acquired immunodeficiency syndrome and disseminated Mycobacterium avium complex (MAC) infection. DESIGN: Phase I study with a 10-day pharmacokinetic phase followed by a 12-week continuation therapy phase. PATIENTS: Twenty-five patients with a median age of 8.3 years were enrolled. Ten were receiving zidovudine and 13 were receiving didanosine at the time of enrollment. INTERVENTION: Clarithromycin suspension was administered to each patient at one of three dose levels: 3.75, 7.5, and 15 mg/kg per dose every 12 hours. Clarithromycin and antiretroviral pharmacokinetics were measured during single-drug and concurrent-drug administration. Clinical and laboratory monitoring was performed biweekly. MEASUREMENTS AND MAIN RESULTS: Clarithromycin was well tolerated at all dose levels. Plasma clarithromycin concentrations increased proportionately with increasing doses, and significant pharmacokinetic interactions were not observed during concurrent administration with zidovudine or didanosine. Decreases in mycobacterial load in blood were observed only at the highest clarithromycin dose level. Decreased susceptibility to clarithromycin developed rapidly (within 12 to 16 weeks) in the majority of MAC strains isolated from study patients.
Assuntos
Infecções Oportunistas Relacionadas com a AIDS/tratamento farmacológico , Claritromicina/uso terapêutico , Complexo Mycobacterium avium , Infecção por Mycobacterium avium-intracellulare/tratamento farmacológico , Infecções Oportunistas Relacionadas com a AIDS/microbiologia , Administração Oral , Adolescente , Criança , Pré-Escolar , Claritromicina/efeitos adversos , Claritromicina/farmacocinética , Feminino , Humanos , Lactente , Masculino , Testes de Sensibilidade Microbiana , Complexo Mycobacterium avium/efeitos dos fármacos , Complexo Mycobacterium avium/isolamento & purificação , Infecção por Mycobacterium avium-intracellulare/microbiologia , RecidivaRESUMO
Human immunodeficiency virus type 1 (HIV-1) isolates from children receiving long-term therapy with an alternating regimen of zidovudine and zalcitabine, or with didanosine monotherapy, were evaluated for resistance to zidovudine, zalcitabine, and didanosine, and for mutations known to be associated with zidovudine or didanosine resistance. HIV-1 from four of six patients receiving zidovudine with zalcitabine developed high-level resistance to zidovudine. A mutation in the HIV-1 reverse transcriptase that is highly associated with zidovudine resistance was identified in all four zidovudine-resistant posttherapy isolates. In contrast, none of the HIV-1 isolates from the seven patients receiving didanosine developed high-level resistance to this agent, despite the identification of a didanosine-associated mutation in six of these posttherapy isolates, although small decreases in sensitivity to didanosine were observed. These results indicate that nucleoside analog-associated mutations in HIV-1 occur frequently in children receiving long-term antiretroviral therapy and that alternating combination therapy does not prevent the development of resistance to zidovudine. They also suggest that there may be differences in the degree of resistance conferred by mutations that result from therapy with different nucleoside analogs. These findings underscore the need for studies to define the clinical importance of these mutations, and for treatment strategies to overcome the emergence of viral resistance in vivo.
Assuntos
Síndrome da Imunodeficiência Adquirida/tratamento farmacológico , Didanosina/antagonistas & inibidores , HIV-1/efeitos dos fármacos , Zalcitabina/antagonistas & inibidores , Zidovudina/antagonistas & inibidores , Síndrome da Imunodeficiência Adquirida/microbiologia , Criança , Pré-Escolar , DNA Viral/genética , Didanosina/administração & dosagem , Resistência Microbiana a Medicamentos , Quimioterapia Combinada , HIV-1/genética , HIV-1/isolamento & purificação , Humanos , Lactente , Testes de Sensibilidade Microbiana/métodos , Mutação , Reação em Cadeia da Polimerase/métodos , Fatores de Tempo , Zalcitabina/administração & dosagem , Zidovudina/administração & dosagemRESUMO
In Brazil, 226 children with cancer presenting 299 episodes of fever and neutropenia (< or = 500/mm3) were treated with two consecutive empirical regimens. Regimen I-Cefoxitin Amikacin-Carbenicillin; and Regimen II Ceftriaxone-Amikacin. 67.0% of the patients had leukemias or lymphomas, documented infections occurred in 47.2%, superinfections occurred in 18.7% (Reg. I) and 17.8% (Reg. II) of the episodes. The most common agents identified in Reg. I and Reg. II were, respectively, Gram negative rods (55.0%) and Gram positive cocci (52.6%). The overall rate of success with modifications (Amphotericin B, Vancomycin, Clindamycin, Metronidazole) was higher in Reg. II (93.0%) than in Reg. I (84.0%). This study shows that the appropriate formula to maximize the successful treatment of children with cancer, fever and neutropenia in developing nations includes adherence to established principles of supportive care, utilizing the optimal antibiotic agents available in the country. It is important to promote the necessary modifications along the treatment having in mind the high index of resistant agents.
Assuntos
Agranulocitose/etiologia , Febre/etiologia , Neoplasias/complicações , Adolescente , Agranulocitose/tratamento farmacológico , Anticorpos/farmacologia , Brasil/epidemiologia , Criança , Pré-Escolar , Estudos de Avaliação como Assunto , Feminino , Febre/tratamento farmacológico , Infecções por Bactérias Gram-Negativas/sangue , Infecções por Bactérias Gram-Negativas/complicações , Infecções por Bactérias Gram-Negativas/tratamento farmacológico , Infecções por Bactérias Gram-Positivas/sangue , Infecções por Bactérias Gram-Positivas/complicações , Infecções por Bactérias Gram-Positivas/tratamento farmacológico , Humanos , Lactente , Masculino , Neoplasias/sangue , Neoplasias/microbiologiaRESUMO
More than 250 children treated at our institution on antiretroviral treatment protocols have been monitored with brain imaging studies. We documented the occurrence and progression of aneurysms of major cerebral arteries in two children with advanced human immunodeficiency virus infection. In both cases these lesions remained clinically silent initially, despite progression to marked dilation.
Assuntos
Infecções por HIV/complicações , HIV-1 , Aneurisma Intracraniano/complicações , Encéfalo/patologia , Angiografia Cerebral , Criança , Didanosina/uso terapêutico , Quimioterapia Combinada , Infecções por HIV/tratamento farmacológico , Humanos , Aneurisma Intracraniano/diagnóstico , Imageamento por Ressonância Magnética , Masculino , Zidovudina/uso terapêuticoRESUMO
We reviewed the 22 cases of Mycobacterium avium-intracellulare (MAI) infection that occurred among 196 human immunodeficiency virus-infected children seen at the National Cancer Institute Pediatric Branch from December 1986 through April 1991, and an additional 65 charts from children with cultures negative for MAI. All patients with proven MAI were receiving antiretroviral therapy with zidovudine, dideoxyinosine, or a combination of zidovudine and dideoxycytidine. All patients had disseminated MAI infection, except one adolescent who had only evidence of localized lymphadenitis. All cases of MAI but one were diagnosed before death. The overall incidence of MAI was 11% in our patients but increased to 24% in patients whose absolute CD4 cell counts were < 100 cells/mm3. Symptoms most commonly associated with MAI infection included recurrent fever (86% of patients), weight loss or failure to thrive (64%), neutropenia (55%), night sweats (32%), and abdominal pain (27%). Children infected with MAI had a mean CD4 percentage of 2% (range, 0% to 7%) and a mean absolute CD4 count of 12 cells/mm3 (range, 0 to 48 cells/mm3), significantly lower than in the remainder of the clinic population or the group of children with cultures negative for MAI. Of 20 patients with MAI infection who were tested, 10 had measurable p24 antigen with a mean value 939 pg/ml (range, 77 to 3270 pg/ml) compared with 19 of 59 patients without MAI infection in whom the mean positive value was 413 pg/ml. There was no difference in survival time between those children with documented MAI infection (median survival time, 45.5 weeks) and those with similarly low CD4 counts and cultures negative for MAI (median survival time, 50.4 weeks). Future improvements in therapeutic options may make screening of pediatric human immunodeficiency virus-infected patients with low CD4 counts a reasonable plan.
Assuntos
Infecções Oportunistas Relacionadas com a AIDS/diagnóstico , Infecção por Mycobacterium avium-intracellulare/diagnóstico , Fatores Etários , Antígenos CD4 , Criança , Pré-Escolar , Feminino , Proteína do Núcleo p24 do HIV/análise , Infecções por HIV/imunologia , Infecções por HIV/transmissão , Humanos , Contagem de Leucócitos , Subpopulações de Linfócitos , Masculino , Fatores de RiscoRESUMO
Bone marrow suppression is the major dose-limiting toxic effect of zidovudine (azidothymidine; AZT) in children with human immunodeficiency virus infection. We evaluated the effect of subcutaneously administered granulocyte colony-stimulating factor (G-CSF) in pediatric patients whose absolute neutrophil count was less than 0.8 x 10(9)/L during AZT therapy despite dosage reductions to 120 mg/m2 every 6 hours. Nineteen patients between 6 months and 20 years of age were treated with AZT and G-CSF and monitored for 2 to 12 months. All had previously shown improvement while receiving AZT but had required dosage reduction or discontinuation. By using a sliding dosing schedule of G-CSF, we attempted to maintain the absolute neutrophil count between 1.5 and 5.0 x 10(9)/L. Administration of G-CSF resulted in a significant increase in the median leukocyte count (2.0 x 10(9)/L to 4.14 x 10(9)/L; p = 0.004), and the median absolute neutrophil count (1.02 x 10(9)/L to 2.96 x 10(9)/L; p = 0.0006). G-CSF was well tolerated, but mild thrombocytopenia developed in nine children. Administration of G-CSF and AZT was discontinued in two patients because of continuing neutropenia. With doses of G-CSF ranging from 1 to 20 micrograms/kg per day, 17 of 19 patients were able to tolerate AZT at a dose of 120 to 180 mg/m2 every 6 hours. We conclude that G-CSF therapy enables patients who have had AZT-related neutropenia to receive therapeutic doses of AZT.
Assuntos
Fator Estimulador de Colônias de Granulócitos/administração & dosagem , Infecções por HIV/terapia , Zidovudina/administração & dosagem , Adolescente , Criança , Pré-Escolar , Quimioterapia Combinada , Feminino , Fator Estimulador de Colônias de Granulócitos/efeitos adversos , Infecções por HIV/sangue , Humanos , Lactente , Contagem de Leucócitos , Masculino , Neutrófilos , Projetos Piloto , Contagem de Plaquetas , Zidovudina/efeitos adversosRESUMO
To evaluate the safety, tolerance, and pharmacokinetics of fluconazole in children with neoplastic diseases, we studied fluconazole in 26 children, aged 5 to 15 years, with normal renal function who were receiving treatment for cancer. The patients received fluconazole, 2, 4, or 8 mg/kg per day for 7 days intravenously for a 2-hour period. Patients had no nausea or vomiting related to fluconazole; three patients had an asymptomatic rise in hepatic aminotransferase values after four to six doses (one patient at 2 mg/kg per day and two patients at 8 mg/kg per day), which returned to normal within 2 weeks after discontinuation of the drug. Fluconazole showed linear first-order kinetics over the dosage range tested and during multiple dosing. After the first dose, mean clearance was 22.8 +/- 2.3 ml/min, volume of distribution 0.87 +/- 0.06 L/kg, and terminal elimination half-life 16.8 +/- 1.1 hours. Similarly, after the last dose, clearance was 19.4 +/- 1.3 ml/min, volume of distribution 0.84 +/- 0.04 L/kg, and terminal elimination half-life 18.1 +/- 1.2 hours. Patients receiving their first fluconazole dose of 8 mg/kg achieved peak serum levels of 9.5 +/- 0.4 microgram/ml and trough levels of 2.7 +/- 0.5 microgram/ml 24 hours later, and an area under the serum concentration-time curve from time zero to infinity of 186 +/- 16 micrograms.hr per milliliter. Renal clearance of fluconazole was 65% +/- 5% of total clearance and demonstrated the predominantly renal excretion of this drug. We suggest that the shorter serum half-life and the higher frequency of aminotransferase elevations in comparison with those of adults warrant careful investigation of fluconazole in controlled clinical trials.
Assuntos
Fluconazol/farmacocinética , Fluconazol/toxicidade , Leucemia Mieloide Aguda/metabolismo , Leucemia-Linfoma Linfoblástico de Células Precursoras/metabolismo , Neoplasias de Tecidos Moles/metabolismo , Criança , Esquema de Medicação , Avaliação de Medicamentos , Feminino , Humanos , Rim/metabolismo , Fígado/metabolismo , Testes de Função Hepática , MasculinoRESUMO
Ganciclovir and foscarnet are both effective for cytomegalovirus retinitis in patients with acquired immunodeficiency syndrome, but the benefits of either agent given alone are limited. A child infected with human immunodeficiency virus who had cytomegalovirus retinitis that progressed despite treatment with either agent alone received the combination of ganciclovir and foscarnet. This treatment resulted in a sustained clinical response.