RESUMO
The objective of this document is to identify and reinforce current recommendations concerning the management of HIV infection in infants and children in the context of good resource availability. All recommendations were graded according to the strength and quality of the evidence and were voted on by the 57 participants attending the first Italian Consensus on Paediatric HIV, held in Siracusa in 2008. Paediatricians and HIV/AIDS care specialists were requested to agree on different statements summarizing key issues in the management of paediatric HIV. The comprehensive approach on preventing mother-to-child transmission (PMTCT) has clearly reduced the number of children acquiring the infection in Italy. Although further reduction of MTCT should be attempted, efforts to personalize intervention to specific cases are now required in order to optimise the treatment and care of HIV-infected children. The prompt initiation of treatment and careful selection of first-line regimen, taking into consideration potency and tolerance, remain central. In addition, opportunistic infection prevention, adherence to treatment, and long-term psychosocial consequences are becoming increasingly relevant in the era of effective antiretroviral combination therapies (ART). The increasing proportion of infected children achieving adulthood highlights the need for multidisciplinary strategies to facilitate transition to adult care and maintain strategies specific to perinatally acquired HIV infection.
Assuntos
Antirretrovirais/uso terapêutico , Infecções por HIV/diagnóstico , Infecções por HIV/tratamento farmacológico , Adulto , Terapia Antirretroviral de Alta Atividade , Criança , Pré-Escolar , Gerenciamento Clínico , Progressão da Doença , Feminino , Infecções por HIV/transmissão , Humanos , Lactente , Recém-Nascido , Transmissão Vertical de Doenças Infecciosas , Itália , GravidezRESUMO
Alemtuzumab is a humanized (IgG(1)) rat monoclonal antibody to CD52 antigen and is currently used in the treatment of chronic lymphocytic leukemia (CLL) and other CD52-positive lymphoproliferative disorders. Various techniques have been developed to measure Alemtuzumab levels in human serum/plasma. The authors report on the validation of a very sensitive enzyme-linked immunosorbent assay (ELISA) to measure serum concentrations of the humanized IgG(1) using a rabbit polyclonal antibody specifically produced against the rat sequence of Alemtuzumab after papain digestion. The assay was successfully applied to test the serum samples of patients with B-lymphocyte CLL who received Alemtuzumab subcutaneously. This ELISA assay could be easily used to determine human serum levels of Alemtuzumab pre- and post-treatment to optimize dosing and scheduling and to study the relationship between dose and clinical response.
Assuntos
Anticorpos Monoclonais/análise , Anticorpos Antineoplásicos/análise , Antineoplásicos/análise , Ensaio de Imunoadsorção Enzimática , Alemtuzumab , Animais , Anticorpos Monoclonais/sangue , Anticorpos Monoclonais Humanizados , Anticorpos Antineoplásicos/sangue , Antineoplásicos/sangue , Relação Dose-Resposta a Droga , Humanos , Leucemia Linfocítica Crônica de Células B/sangue , Coelhos , RatosRESUMO
New immunosuppressive strategies that can prevent both acute and chronic rejection are being investigated to achieve graft tolerance and to minimize side effects and toxicity that may lead to graft loss. Drug pharmacokinetics and pharmacodynamics, as well as pharmacogenetics, all play a role in customizing treatment to the individual patient. To improve patient compliance, new drug formulations are on trial, such as the modified- release oral form of tacrolimus MR4 for once daily administration, which seems to be equivalent to bid administration in terms of steady-state exposure. Monoclonal/polyclonal antibodies are increasingly used in the induction phase in protocols where steroids are discontinued early. However, discontinuing steroids carries a high risk of acute rejection or organ failure in some subgroups of patients. The supposed benefit of steroid discontinuation may not be enjoyed by all patients. Minimizing anticalcineurin agents may prove to be similarly or even more advantageous. The use of new drugs and new combinations has greatly improved short-term transplant outcomes. The new goal is, therefore, to improve long-term results and particularly to prevent chronic rejection, thus increasing patient and organ survival.
Assuntos
Terapia de Imunossupressão/tendências , Imunossupressores/uso terapêutico , Imunologia de Transplantes , Humanos , Terapia de Imunossupressão/métodos , Imunossupressores/farmacocinética , Transplante de Rim/imunologia , Transplante de Fígado/imunologiaRESUMO
Options for relapsed/refractory indolent lymphoma include chemotherapy, immunotherapy and high-dose therapy with autologous support. The best combination of these approaches, however, is not defined. We treated 10 patients with relapsed/refractory follicular (n = 7) or mantle cell lymphoma (n = 3) using chemotherapy, immunotherapy, high-dose therapy and autotransplant in a sequence of four phases, each designed to play a specific role in tumour eradication. After the debulking with VACOP-B (doxorubicin, cyclophosphamide, etoposide, vincristine, prednisone, bleomycin) (phase 1), 9/10 patients responded but none achieved a molecular response. After the immuno-chemotherapy phase, which combined Rituximab with vincristine and cyclophosphamide, seven patients were in complete response (CR) and three in good partial response (PR), and all those with a molecular marker of disease showed a disappearance of the signal from marrow and blood. Phase 3, which coupled high-dose cytarabine with Rituximab, was effective in mobilizing an adequate number of progenitor cells that were polymerase chain reaction negative in all informative cases. Phase 4 consisted of high-dose therapy with autologous support followed by two doses of Rituximab. Autograft was performed in nine patients. The haematopoietic recovery was as expected. This sequence of chemotherapy, immuno-chemotherapy, stem cell mobilization with in vivo purging and autotransplant, organized in four blocks of treatment, was simple to administer and devoid of toxic effects. It permits rapid attainment of clinical and molecular response and enables the harvest of lymphoma-free peripheral blood progenitor cells even in heavily pretreated patients with relapsed or refractory disease.
Assuntos
Anticorpos Monoclonais/uso terapêutico , Antineoplásicos/uso terapêutico , Purging da Medula Óssea , Mobilização de Células-Tronco Hematopoéticas , Transplante de Células-Tronco Hematopoéticas , Linfoma/terapia , Adulto , Anticorpos Monoclonais/farmacocinética , Anticorpos Monoclonais Murinos , Antineoplásicos/farmacocinética , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Bleomicina/administração & dosagem , Ciclofosfamida/administração & dosagem , Citarabina/administração & dosagem , Doxorrubicina/administração & dosagem , Etoposídeo/administração & dosagem , Feminino , Rearranjo Gênico , Genes bcl-2 , Meia-Vida , Humanos , Linfoma Folicular/terapia , Linfoma de Célula do Manto/terapia , Masculino , Taxa de Depuração Metabólica , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase , Prednisona/administração & dosagem , Recidiva , Rituximab , Transplante Autólogo , Vincristina/administração & dosagemAssuntos
Acetamidas/líquido cefalorraquidiano , Anti-Infecciosos/líquido cefalorraquidiano , Antibioticoprofilaxia , Infecções do Sistema Nervoso Central/líquido cefalorraquidiano , Oxazolidinonas/líquido cefalorraquidiano , Complicações Pós-Operatórias/líquido cefalorraquidiano , Acetamidas/farmacocinética , Acetamidas/uso terapêutico , Anti-Infecciosos/farmacocinética , Anti-Infecciosos/uso terapêutico , Infecções do Sistema Nervoso Central/tratamento farmacológico , Humanos , Linezolida , Meningites Bacterianas/líquido cefalorraquidiano , Meningites Bacterianas/tratamento farmacológico , Oxazolidinonas/farmacocinética , Oxazolidinonas/uso terapêutico , Complicações Pós-Operatórias/microbiologiaRESUMO
OBJECTIVE: To compare the plasma pharmacokinetics of lamivudine 150mg twice daily and 300mg once daily in patients with HIV-1 infection. DESIGN: Nonblind, sequential, pharmacokinetic study. PARTICIPANTS: 13 patients with HIV-1 infection (median age 36 years). METHODS: Patients were tested during twice daily and then once daily regimens of lamivudine. In both regimens, the total daily dose of lamivudine was identical (300 mg/day). Blood samples for pharmacokinetic analysis were taken over a 12-hour period after > or =7 days of twice daily administration, and again over a 24-hour period after 7 days of once daily administration,. RESULTS: 12 patients completed the study. Lamivudine pharmacokinetic parameters (mean +/- SD) after administration of 150mg twice daily were: peak plasma concentration (Cmax) 2077+/-816 microg/L; trough plasma concentration (Cmin) 332+/-219 microg/L; elimination half-life (t 1/2beta) 6.1+/-1.9h; time to Cmax (t(max)) 1.6+/-0.7h; average concentration over the dosage interval (Cav) 711+/-269 microg/L; and area under the concentration-time curve (AUC) over 2 dosage intervals (24h) 17085+/-6464 microg x h/L. Corresponding values after administration of 300mg once daily were: Cmax 3461+/-854 microg/L; Cmin 146+/-87 microg/L; t1/2 7.9+/-3.4h; t(max) 2.2+/-1.3h; Cav 705+/-177 microg/L; and AUC over 1 dosage interval (24h) 16644+/-4150 microg x h/L. Statistical analysis showed a significant difference (p < 0.05) between the 2 schedules for Cmax and Cmin values, whereas no significant differences emerged for the other parameters. CONCLUSIONS: Once daily lamivudine leads to a similar exposure in plasma as twice daily administration of the same total daily dose. Since once daily administration may result in improved compliance, these results provide the pharmacokinetic basis for using lamivudine in a once daily regimen. Randomised clinical studies are needed to confirm this pharmacokinetic finding.
Assuntos
Fármacos Anti-HIV/farmacocinética , Infecções por HIV/metabolismo , HIV-1 , Lamivudina/farmacocinética , Adulto , Fármacos Anti-HIV/administração & dosagem , Fármacos Anti-HIV/sangue , Área Sob a Curva , Cromatografia Líquida de Alta Pressão , Esquema de Medicação , Feminino , Infecções por HIV/sangue , Meia-Vida , Humanos , Lamivudina/administração & dosagem , Lamivudina/sangue , MasculinoRESUMO
An analytical technique using liquid chromatography (LC) coupled with electrospray-mass spectrometry (ESI--MS) has been developed for the simultaneous determination of five protease inhibitors (PIs): saquinavir, indinavir, ritonavir, nelfinavir, and amprenavir; and three non-nucleoside reverse transcriptase inhibitors (NNRTIs): nevirapine, delavirdine, and efavirenz, in human plasma. This assay allows the elution and identification of these drugs in a single run (10 minutes) using a linear gradient with water and acetonitrile. The procedure involves liquid--liquid extraction. High-performance liquid chromatography (HPLC) separation was achieved on a C18 reversed-phase column, with a linear gradient elution followed by mass spectrometry detection. The calibration curves, obtained by automatic process peak area integration, show a good linearity in a range of concentrations between 20 and 10,000 ng/mL (40--10,000 ng/mL for efavirenz). The limit of detection was approximately 10 ng/mL for seven drugs (25 ng/mL for efavirenz). The coefficients of variation (CV) were always less than 15% for both intraday and interday precision for each compound. The recovery of the eight drugs ranged from 88.5% to 100%. This novel LC/ESI--MS assay provides an excellent method for simultaneous quantitative monitoring of different components of the highly active antiretroviral treatments (HAARTs) in patients treated simultaneously with PIs and NNRTIs, and it has been successfully applied to therapeutic drug monitoring and pharmacokinetic studies.
Assuntos
Cromatografia Líquida/métodos , Inibidores da Protease de HIV/sangue , Espectrometria de Massas/métodos , Inibidores da Transcriptase Reversa/sangue , Alcinos , Benzoxazinas , Carbamatos , Ciclopropanos , Delavirdina/sangue , Monitoramento de Medicamentos , Furanos , Humanos , Indinavir/sangue , Nelfinavir/sangue , Nevirapina/sangue , Oxazinas/sangue , Reprodutibilidade dos Testes , Ritonavir/sangue , Saquinavir/sangue , Sensibilidade e Especificidade , Sulfonamidas/sangueRESUMO
The purpose of this study was to evaluate the pharmacokinetics (PK) profile of oral levofloxacin in human immunodeficiency virus-positive patients in steady-state treatment with nelfinavir (NFV) or with efavirenz (EFV) and to determine the effects of levofloxacin on the PK parameters of these two antiretroviral agents. For levofloxacin, plasma samples were obtained at steady state during a 24-h dosing interval. Plasma NFV and EFV concentrations were evaluated before and after 4 days of levofloxacin treatment. Levofloxacin PK do not seem affected by NFV and EFV. There was no significant difference between NFV and EFV plasma levels obtained with and without levofloxacin.
Assuntos
Anti-Infecciosos/farmacocinética , Infecções por HIV/metabolismo , Levofloxacino , Ofloxacino/farmacocinética , Administração Oral , Alcinos , Fármacos Anti-HIV/farmacologia , Fármacos Anti-HIV/uso terapêutico , Benzoxazinas , Estudos de Coortes , Ciclopropanos , Interações Medicamentosas , Infecções por HIV/tratamento farmacológico , Humanos , Nelfinavir/farmacologia , Nelfinavir/uso terapêutico , Oxazinas/farmacologia , Oxazinas/uso terapêutico , Estudos ProspectivosAssuntos
Transplante de Coração/fisiologia , Imunossupressores/farmacocinética , Tacrolimo/farmacocinética , Adulto , Soro Antilinfocitário/uso terapêutico , Azatioprina/uso terapêutico , Peso Corporal , Quimioterapia Combinada , Feminino , Transplante de Coração/imunologia , Humanos , Imunossupressores/sangue , Imunossupressores/uso terapêutico , Testes de Função Renal , Testes de Função Hepática , Masculino , Pessoa de Meia-Idade , Período Pós-Operatório , Análise de Regressão , Tacrolimo/sangue , Tacrolimo/uso terapêutico , Fatores de TempoRESUMO
The pharmacokinetics of nelfinavir tablets (A) and an oral simplified nelfinavir suspension (B) were studied. Twelve healthy volunteers randomly received either five 250-mg nelfinavir tablets or a simplified oral suspension obtained from tablets dissolved in water (nelfinavir 1250 mg in 100 mL of water) in a single dose before being crossed over to the second treatment after a one-week washout period. Blood samples were drawn up to 24 h after drug administration. Nelfinavir concentrations in plasma were analyzed by a specific and validated reverse-phase high-performance liquid chromatography assay (HPLC) with UV detection, and pharmacokinetic values were determined. For the AUC(0-infinity) with means+/-SD of 31.71+/-7.85, 30.88+/-10.28 (microg/L) respectively for treatments B and A, the ratio (F(B/A)) was of 1.1 with a C.I. of 0.90-1.24. For Cmax with means+/-SD of 3.1+/-0.6 (treatment B) and 3.2+/-0.8 mg/mL (treatment A), the ratio was 1.0. with C.I. of 0.92-1.08. The two treatments evidenced no significant differences in AUC(0-inifnity) and Cmax values and the two-one sided t-test showed that the two preparations are bioequivalent. There was no significant difference in Tmax between the liquid and tablets. Nelfinavir suspension might be a option for treating HIV-infected patients with swallowing disturbances or compliance problems.
Assuntos
Inibidores da Protease de HIV/farmacocinética , Nelfinavir/farmacocinética , Administração Oral , Adulto , Terapia Antirretroviral de Alta Atividade , Área Sob a Curva , Química Farmacêutica , Cromatografia Líquida de Alta Pressão , Excipientes , Feminino , Infecções por HIV/tratamento farmacológico , Inibidores da Protease de HIV/administração & dosagem , Humanos , Cinética , Masculino , Nelfinavir/administração & dosagem , Cooperação do Paciente , Comprimidos , Equivalência TerapêuticaRESUMO
The authors performed a comparative analysis of 60 whole blood samples containing cyclosporine (CsA) from heart transplant (HTx) recipients (n = 60) by the two "specific" monoclonal immunoassays, enzyme-multiplied immunoassay technique (EMIT) and fluorescence polarization immunoassay (S-FPIA), using the Altman-Bland approach based on graphical techniques and simple calculations. The CsA blood concentrations measured by S-FPIA [mean (SD): 268.1 (108.8) ng/mL] showed a statistically significant difference (P < 0.001) from the corresponding concentrations measured by EMIT [219.6 (118.7) ng/mL]. The CsA concentrations were 27% (median) higher when determined by monoclonal S-FPIA than by EMIT. The comparison between EMIT and S-FPIA showed a good correlation (S-FPIA conc. (ng/mL) = EMIT conc. (ng/mL) x 0.88 + 76.1, r = 0.96, P < 0.001). However, a high correlation does not mean that the two methods agree, and their use as interchangeable might be misleading. The authors summarized the degree of agreement by calculating the bias estimated by the mean difference (d) and the standard deviation of the difference (SD). For CsA concentration data, the mean difference (S-FPIA minus EMIT) is +49.9 ng/mL and SD is 31.2 ng/mL. Altman-Bland analysis indicates considerable lack of agreement between EMIT and S-FPIA, with discrepancies of more than 100 ng/mL. The present study's data clearly show that there is a considerable and clinically unacceptable lack of agreement between the S-FPIA and the EMIT techniques in HTx recipients for the whole range of concentrations evaluated (25-500 ng/mL), and this is caused by the variation in the overestimation of the CsA parent compound. Even though a similar CsA reference range was reported during maintenance therapy for both methods (150-250 ng/mL), which might encourage their interchangeability in the clinical setting, this approach should be avoided. Laboratory reports should always state both the concentration of CsA and the analytical method.
Assuntos
Ciclosporina/sangue , Monitoramento de Medicamentos/métodos , Transplante de Coração , Imunossupressores/sangue , Adulto , Idoso , Anticorpos Monoclonais , Especificidade de Anticorpos , Técnica de Imunoensaio Enzimático de Multiplicação , Imunoensaio de Fluorescência por Polarização , Humanos , Pessoa de Meia-Idade , Reprodutibilidade dos TestesAssuntos
Inibidores da Protease de HIV/farmacocinética , Indinavir/farmacocinética , Vacinas contra Influenza/imunologia , Síndrome da Imunodeficiência Adquirida/tratamento farmacológico , Adulto , Terapia Antirretroviral de Alta Atividade , Feminino , Humanos , Imunização , Masculino , Pessoa de Meia-IdadeRESUMO
Rituximab is a chimeric monoclonal antibody (MAb) directed against the B-cell CD20 antigen that has been approved for therapy of relapsed and resistant follicular non-Hodgkin's lymphoma (NHL). This study describes the development and validation of a highly sensitive, rapid, accurate, precise enzyme-linked immunosorbent assay (ELISA) to measure Rituximab serum concentrations. This study also describes the application of the ELISA method to a pharmacokinetic study in a homogeneous group of patients with follicular lymphoma who received 4 weekly doses of MAb at the standard dose of 375 mg/m2 as consolidation of chemotherapy. In the patients in this study, the median Rituximab serum concentrations increased during therapy, and showed a slow decline during the posttreatment period. The Rituximab elimination half-life of approximately 20 days accounts for the demonstrated accumulation of MAb in serum samples. Because previous pharmacokinetic studies showed a correlation between Rituximab serum levels and tumor response, the ELISA method used in this study, which allows a precise control of serum concentrations, could be useful for predicting the final response to the MAb and for selecting patients able to benefit from higher dosage or repeated drug administration.
Assuntos
Anticorpos Monoclonais/sangue , Antineoplásicos/sangue , Ensaio de Imunoadsorção Enzimática/métodos , Linfoma Folicular/sangue , Anticorpos Monoclonais/farmacocinética , Anticorpos Monoclonais/uso terapêutico , Anticorpos Monoclonais Murinos , Antineoplásicos/farmacocinética , Antineoplásicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Compartimentos de Líquidos Corporais , Ciclofosfamida/administração & dosagem , Doxorrubicina/administração & dosagem , Esquema de Medicação , Estabilidade de Medicamentos , Humanos , Infusões Intravenosas , Linfoma Folicular/tratamento farmacológico , Linfoma Folicular/metabolismo , Prednisona/administração & dosagem , Reprodutibilidade dos Testes , Rituximab , Sensibilidade e Especificidade , Vincristina/administração & dosagemRESUMO
Nelfinavir is a novel protease inhibitor that exhibits good inhibitory activity against human immunodeficiency virus type 1 (HIV-1) and is currently used in combination with reverse transcriptase inhibitors for the management of HIV infection. In this study we analysed the pharmacokinetic profile of nelfinavir after multiple oral doses in 18 HIV-infected patients during a combination regimen of nelfinavir plus efavirenz and stavudine. Patients who received the study drug for >/=4 weeks were considered for pharmacokinetic evaluation. Blood samples were obtained at the following times: 0 (before nelfinavir administration), 1, 2, 3, 4, 6 and 8 h after administration. Nelfinavir plasma concentrations were analysed by a specific and validated HPLC assay with ultraviolet detection. Nelfinavir concentration-time data were analysed by compartmental and non-compartmental techniques and the pharmacokinetic parameters of nelfinavir were determined according to a one-compartment model. We found a high variability between individuals in nelfinavir plasma concentrations. The mean average drug plasma concentration was 2.22 +/- 1.25 mg/L and the mean AUC during the dosing interval was 17.7 +/- 10.0 mg*h/L. The mean nelfinavir trough plasma concentration was 1.58 +/- 1.0 mg/L. A good relationship was found between AUC(0-8h) and the plasma concentrations measured at 6 h, and the trough plasma concentrations made total body exposure for nelfinavir less predictable. Alternatively, a 2 h abbreviated AUC provides a good estimate of the full AUC(0-8h). Comparing the pharmacokinetic parameters obtained in our patients with those reported for patients receiving nelfinavir monotherapy or nelfinavir combined with nucleoside analogues, one observes substantial overlap with nelfinavir concentrations achieved without efavirenz.
Assuntos
Fármacos Anti-HIV/farmacocinética , Infecções por HIV/metabolismo , HIV-1 , Nelfinavir/farmacocinética , Oxazinas/farmacocinética , Estavudina/farmacocinética , Adulto , Alcinos , Fármacos Anti-HIV/uso terapêutico , Área Sob a Curva , Benzoxazinas , Cromatografia Líquida de Alta Pressão , Estudos de Coortes , Ciclopropanos , Quimioterapia Combinada , Feminino , Infecções por HIV/tratamento farmacológico , Humanos , Masculino , Nelfinavir/uso terapêutico , Oxazinas/uso terapêutico , Estavudina/uso terapêuticoRESUMO
AIMS: To define the pharmacokinetic profile of efavirenz (EFV) in HIV-1 infected patients, when administered alone or with nelfinavir (NFV). METHODS: Eleven HIV-positive patients, in steady-state treatment with EFV and 11 patients in steady-state treatment with EFV+NFV, were evaluated. Blood samples for pharmacokinetic analysis were obtained during a dosage interval. Plasma concentrations of EFV were determined by h.p.l.c. RESULTS: No significant difference was found between the principal pharmacokinetic parameters of EFV when administered alone or in combination with NFV (mean AUC: 57.1-7727.3 vs 60.9+/-12.3 microg ml-1 h; mean CL/F: 0.18+/-0.072 vs 0.16+/-0.04 l h-1 kg-1; mean Cmax: 4.0+/-1.7 vs 4.3+/-1.2 microg ml-1, and mean tmax: 4.1+/-1.7 vs 3.5+/-0.5 h) Mean trough plasma concentrations (C0) of EFV were 1.64+/-0.93 microg ml-1, with and without NFV. A good correlation was found between C0 and AUC(0,24h) (r=0.96; P<0. 01). CONCLUSIONS: Despite the common metabolic pathway, there was no significant influence of NFV on the pharmacokinetics of EFV. EFV exhibits a relatively low interindividual variability and a dosing regimen of 600 mg day-1 assures plasma concentrations that are adequate for inhibition of viral replication.
Assuntos
Fármacos Anti-HIV/farmacocinética , Infecções por HIV/metabolismo , HIV-1 , Nelfinavir/farmacocinética , Oxazinas/farmacocinética , Adulto , Alcinos , Área Sob a Curva , Benzoxazinas , Cromatografia Líquida de Alta Pressão , Ciclopropanos , Feminino , Humanos , Masculino , Espectrofotometria UltravioletaAssuntos
Antibióticos Antineoplásicos/farmacocinética , Neoplasias da Mama/tratamento farmacológico , Epirubicina/farmacocinética , Doença de Gilbert/complicações , Adulto , Antibióticos Antineoplásicos/administração & dosagem , Área Sob a Curva , Neoplasias da Mama/complicações , Relação Dose-Resposta a Droga , Esquema de Medicação , Epirubicina/administração & dosagem , Feminino , Seguimentos , Humanos , Neoplasias Hepáticas/secundário , Resultado do TratamentoAssuntos
Fármacos Anti-HIV/farmacocinética , Infecções por HIV/tratamento farmacológico , Hepatopatias/complicações , Nelfinavir/farmacocinética , Oxazinas/farmacocinética , Adulto , Alcinos , Fármacos Anti-HIV/uso terapêutico , Benzoxazinas , Ciclopropanos , Quimioterapia Combinada , Feminino , Infecções por HIV/sangue , Infecções por HIV/complicações , Inibidores da Protease de HIV/farmacocinética , Inibidores da Protease de HIV/uso terapêutico , Humanos , Hepatopatias/sangue , Masculino , Nelfinavir/uso terapêutico , Oxazinas/uso terapêutico , Inibidores da Transcriptase Reversa/farmacocinética , Inibidores da Transcriptase Reversa/uso terapêutico , Estavudina/uso terapêuticoRESUMO
Efavirenz (EFV, DMP-266) is a new antiretroviral agent belonging to the class of nonnucleoside reverse transcriptase inhibitors. It has recently been approved by the Food and Drug Administration in management of human immunodeficiency virus (HIV). Preliminary pharmacokinetic studies on EFV in healthy volunteers show that the drug may influence the metabolism of protease inhibitors. For the determination of EFV in human plasma, a validated and specific reverse-phase high-performance liquid chromatography (HPLC) method, with UV detection, was developed. We used 100 microL plasma sample for a liquid-liquid extraction with diethyl ether after basification. The mobile phase was a mixture of acetonitrile and water, pumped at a flow rate of 1.2 mL/min. Ultraviolet detection was carried out at a wavelength of 247 nm. Retention times for EFV and internal standard (IS) were 5.3 and 4.5 minutes, respectively, and there was no chromatographic interference from other commonly administered drugs. The limit of detection was 100 ng/mL. The described assay is a rapid and accurate method for measurement of EFV in plasma: the easy preparation and small sample size makes this assay highly suitable for pharmacokinetic studies and routine clinical analysis in patients with HIV. In addition, the reproducibility of the method is only moderately increased by including IS, so analyzing without IS may be an alternative.
Assuntos
Fármacos Anti-HIV/sangue , Cromatografia Líquida de Alta Pressão/métodos , Oxazinas/sangue , Inibidores da Transcriptase Reversa/sangue , Administração Oral , Alcinos , Benzoxazinas , Ciclopropanos , Humanos , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Fatores de Tempo , Raios UltravioletaRESUMO
AIMS: To investigate the pharmacokinetic profile of the protease inhibitor saquinavir (SQV) after multiple doses in HIV-positive patients and to evaluate the possibility of predicting total body exposure of SQV from concentrations determined at single time points. METHODS: Twenty HIV-positive patients on steady-state treatment with SQV (Hard-Gel-Capsule, Invirase(R)) were enrolled in this study. Serial blood samples were obtained during a dosing interval. SQV plasma concentrations were determined by high performance liquid chromatography (h.p.l.c.) and pharmacokinetic parameters were determined by noncompartmental techniques. RESULTS: There was a marked interindividual variability in SQV pharmacokinetic parameters with a 11-fold variability in total systemic exposure to SQV, as expressed by AUC(0,8h) values (range: 268-3009 ng ml-1 h, CV: 69%). The oral clearance shows an interindividual CV of 75%. A strong correlation (r=0.94) was found between SQV plasma concentration at 3 h (C3 h ) and AUC(0,8h). CONCLUSIONS: This study shows that C3 h is a good predictor for total body exposure of SQV and might be useful to predict SQV disposition in HIV-positive patients on steady-state treatment.
Assuntos
Síndrome da Imunodeficiência Adquirida/tratamento farmacológico , Monitoramento de Medicamentos , HIV-1 , Saquinavir/farmacocinética , Síndrome da Imunodeficiência Adquirida/metabolismo , Adolescente , Adulto , Idoso , Humanos , Pessoa de Meia-IdadeRESUMO
Recently all-trans retinoic acid, an oxidation product of retinol, has become famous, since it is a component of "retinoids solution" of "Di Bella's therapy". Since all-trans retinoic acid is rapidly destroyed in the presence of light and oxidants, we verified its stability in samples of "retinoids solution" stored in conditions believed optimal (under stream of nitrogen) and we compare the obtained results with those observed in other "retinoids solution" samples daily open and close again, simulating the intake from the patient. All samples showed a decrease of all-trans retinoic acid recovery at the end of the study, with a more rapid decline in samples daily open. From our observations, we decided to indicate an expiration date of one months from the date of "solution" preparation. The patient's manipulation brings out a change in the final composition of "retinoids solution".