RESUMO
This article describes a differential pulse voltammetric (DPV) method for the determination of diclofenac in pharmaceutical preparations and human serum. The proposed method was based on electro-oxidation of diclofenac at platinum electrode in 0.1 M TBAClO4/acetonitrile solution. The well-defined two oxidation peaks were observed at 0.87 and 1.27 V, respectively. Calibration curves that obtained by using current values measured for second peak were linear over the concentration range of 1.5-17.5 μg mL-1and 2-20 μg mL-1 in supporting electrolyte and serum, respectively. Precision and accuracy were also checked in all media. Intra- and inter-day precision values for diclofenac were less than 3.87, and accuracy (relative error) was better than 4.12%. The method developed in this study is accurate, precise and can be easily applied to Diclomec, Dicloflam and Voltaren tablets as pharmaceutical preparation. In addition, the proposed technique was successfully applied to spiked human serum samples. No electro-active interferences from the endogenous substances were found in human serum...
Este artigo descreve um método de voltametria de pulso diferencial (VPD) para a determinação de diclofenaco em preparações farmacêuticas e em soro humano. O método proposto foi baseado em eletroxidação de diclofenaco no eléctrodo de platina em solução 0,1 M TBAClO4/acetonitrila. Dois picos de oxidação bem definidos foram observados em 0,87 e 1,27 V, respectivamente. As curvas de calibração obtidas utilizando-se valores de corrente medidos por segundo pico foram lineares no intervalo de concentração de 1,5-17,5 μg mL-1e 2-20 μg mL-1em eletrólito suporte e soro, respectivamente. Precisão e exatidão também foram verificadas em todos os meios. Valores de precisão intra- e inter-dia para o diclofenaco foram inferiores a 3.87 e a precisão (erro relativo) foi melhor do que 4,12%. O método desenvolvido neste estudo é exato, preciso e pode ser facilmente aplicado a Diclomec, Dicloflam e comprimidos Voltaren, como preparação farmacêutica. Além disso, a técnica proposta foi aplicada com sucesso em amostras de soro humano. Não se observaram interferências das substâncias endógenas no soro humano...
Assuntos
Humanos , Diclofenaco/análise , Diclofenaco/farmacologia , Diclofenaco/sangue , Testes de Química Clínica/métodos , Química Farmacêutica/métodos , Técnicas Eletroquímicas/métodosRESUMO
PURPOSE: There is evidence that the sulfonylurea antidiabetic agent glibenclamide reduces the analgesic action of non-steroidal anti-inflammatory drugs (NSAIDs), opioids and neuromodulators in animal models. Therefore, in view of the vast clinical uses and interactions of NSAIDs with commonly used therapeutic agents, the interaction of the NSAID diclofenac and glibenclamide was investigated about pharmacokinetic profile and antinociceptive effect in rats. METHODS: Antinociception was assessed using the formalin test. Fifty microliters of diluted formalin was injected s.c. into the dorsal surface of the right hind paw. Nociceptive behavior was quantified as the number of flinches of the injected paw during 60 min after injection. Rats were treated with oral administration of vehicle or increasing doses of diclofenac (3-18 mg/kg) before formalin injection. To determine the pharmacodynamic interaction between diclofenac and glibenclamide, the effect of oral administration of glibenclamide (1-30 mg/kg) on the antinociceptive effect induced by diclofenac (18 mg/kg, p.o.) was assessed. To evaluate the pharmacokinetic interaction between diclofenac and glibenclamide, the effect of glibenclamide (10 mg/kg, p.o.) on the pharmacokinetic of diclofenac (18 mg/kg, p.o.) was studied in the rat. Blood samples were taken over 8 h and analyzed using a validated high-performance liquid chromatography method to generate the pharmacokinetic profile of diclofenac. Pharmacokinetic parameters were estimated using noncompartmental analysis. RESULTS: Systemic administration of diclofenac produced a dose-dependent antinociceptive effect in the formalin test. Systemic treatment with glibenclamide prevented diclofenac-induced antinociception. In pharmacokinetic interaction study, no significant (P>0.05) change in diclofenac concentration-time profiles in the presence of glibenclamide was detected. CONCLUSION: The experimental findings suggest that systemic glibenclamide is able to block the diclofenac-induced antinociception in the rat formalin test. Besides, this antagonism was not produced by diminution in the bioavailability of diclofenac. Likewise, the validated assay had sufficient accuracy and precision for pharmacokinetic determination of diclofenac in the rat.
Assuntos
Anti-Inflamatórios não Esteroides/farmacocinética , Diclofenaco/farmacocinética , Glibureto/farmacologia , Hipoglicemiantes/farmacologia , Canais KATP/antagonistas & inibidores , Bloqueadores dos Canais de Potássio/farmacologia , Animais , Anti-Inflamatórios não Esteroides/antagonistas & inibidores , Anti-Inflamatórios não Esteroides/sangue , Anti-Inflamatórios não Esteroides/farmacologia , Cromatografia Líquida de Alta Pressão , Diclofenaco/antagonistas & inibidores , Diclofenaco/sangue , Diclofenaco/farmacologia , Relação Dose-Resposta a Droga , Interações Medicamentosas , Feminino , Glibureto/administração & dosagem , Hipoglicemiantes/administração & dosagem , Limite de Detecção , Dor/tratamento farmacológico , Medição da Dor , Bloqueadores dos Canais de Potássio/administração & dosagem , Ratos , Ratos WistarRESUMO
Eight male cattle were given a combined dose containing 20 mg/kg oxytetracycline and 0.5 mg/kg diclofenac intramuscularly. Blood samples were drawn at different times until 168 h after administration. Two experimental animals were slaughtered by humane means at weekly intervals up to 28 days after administration. Samples of muscle, injection zone tissue, liver, kidney and fat were obtained. Oxytetracycline and diclofenac concentrations were determined by high performance liquid chromatography. Kinetic analysis was performed by linear regression using the CSTRIP programme. Plasma oxytetracycline concentration showed a maximum (Cmax) of 3.89 +/- 1.48 microg/ml and a prolonged elimination half-life (T1/2beta: 47.73 +/- 18.33 h). The diclofenac plasma profile showed high Cmax (577.62 +/- 238.40 ng/ml), and its T1/2beta was also prolonged (30.48 +/- 9.42 h). Oxytetracycline concentrations were measurable in liver and adipose tissue until day 21 after administration, but all tissue samples were negative for diclofenac at 21 days. The long elimination half-life of diclofenac was an unexpected finding; its T1/2beta in humans is 1.1 h.
Assuntos
Antibacterianos/farmacocinética , Anti-Inflamatórios não Esteroides/farmacocinética , Bovinos/metabolismo , Diclofenaco/farmacocinética , Oxitetraciclina/farmacocinética , Animais , Antibacterianos/sangue , Anti-Inflamatórios não Esteroides/sangue , Área Sob a Curva , Cromatografia Líquida de Alta Pressão/métodos , Cromatografia Líquida de Alta Pressão/veterinária , Diclofenaco/sangue , Meia-Vida , Injeções Intramusculares/veterinária , Modelos Lineares , Masculino , Especificidade de Órgãos , Oxitetraciclina/sangue , Distribuição TecidualRESUMO
The aim of this study was to evaluate the effect of sodium diclofenac on the bioavailability of amoxicillin. In this randomised, crossover study with a 1-week washout period, 20 volunteers received a 2g oral dose of amoxicillin (Amoxil) (Group 1) or a 2g oral dose of amoxicillin with 100 mg of sodium diclofenac (Voltaren) (Group 2). Blood samples were collected at 0, 0.25, 0.5, 1, 1.5, 2, 2.5, 4, 6, 8, 12 and 24h following drug administration. High-performance liquid chromatography with ultraviolet detection was used to quantify plasma amoxicillin concentrations. Bioassay (Micrococcus luteus ATCC 9341) was performed to verify the antimicrobial efficacy of amoxicillin in vitro. The pharmacokinetic parameters area under the plasma concentration-time curve (AUC), maximum plasma concentration observed during the 24-h study period (C(max)) and renal clearance (CL) were analysed by analysis of variance, and time at which C(max) occurred (T(max)) and volume of distribution (VD) were analysed by Wilcoxon test (P<0.05). For Group 1, the mean (+/- standard deviation) AUC(0-24), C(max) and T(max) values were 3391.8+/-1186.7 microg min/mL, 17.3+/-6.5 microg /mL and 121.5+/-20.6 min, respectively; and for Group 2, the values were 2918.4+/-1024.8 microg min/mL, 15.5+/-5.8 microg /mL and 136.5+/-30.0 min, respectively. Lower values of AUC and C(max) were observed for Group 2 (P<0.05). CL of amoxicillin increased (P< 0.05) by 18.5% in Group 2, suggesting that sodium diclofenac may interfere with amoxicillin renal excretion. In conclusion, sodium diclofenac can significantly reduce the bioavailability of amoxicillin.
Assuntos
Amoxicilina/farmacocinética , Diclofenaco/farmacologia , Adulto , Amoxicilina/sangue , Disponibilidade Biológica , Estudos Cross-Over , Diclofenaco/sangue , Diclofenaco/farmacocinética , Interações Medicamentosas , Humanos , MasculinoRESUMO
Many patients with hypertension, particularly elderly patients, take nonsteroidal antiinflammatory drugs (NSAIDs) and antihypertensive agents. However, few studies describe the effect of the association of antihypertensive agents with NSAIDs on inflammatory response in hypertension. To investigate this, spontaneously hypertensive rats (SHRs) were treated with either diclofenac alone or diclofenac combined with losartan (an AT1 angiotensin II antagonist). The leukocyte-endothelial interaction was then observed using intravital microscopy. Blood pressure of SHR (169.6+/-3.6) was increased by diclofenac (186.4+/-2.9), reduced by losartan (152.6+/-3.5), and reduced by the combination of the 2 (158.9+/-3.7). All the treatments tested reduced the number of rollers, adherent and migrated leukocytes, and the expression of endothelial intercellular adhesion molecule-1 and P-selectin. The association of losartan reduced the effect of diclofenac on leukocyte migration. Neither treatment tested increased the venular shear rate or modified the venular diameters, number of circulating leukocytes, and L-selectin expression on granulocytes. The reduction of CD11/CD18 expression induced by diclofenac alone was hindered by losartan. A pharmacokinetic interference between losartan and diclofenac was ruled out since no significant differences were observed in the plasma concentrations of each drug when they were associated. In conclusion, although diclofenac does not interfere with the losartan antihypertensive effect, losartan attenuates the effect of diclofenac has on leukocyte behavior and expression of adhesion molecules. Losartan has an antimigratory effect, reducing leukocyte migration by reducing ICAM-1 and P-selectin expression. Losartan may hinder the full expression of the antimigratory effect of diclofenac.
Assuntos
Anti-Inflamatórios não Esteroides/uso terapêutico , Anti-Hipertensivos/uso terapêutico , Diclofenaco/uso terapêutico , Hipertensão/tratamento farmacológico , Migração e Rolagem de Leucócitos/efeitos dos fármacos , Losartan/uso terapêutico , Animais , Anti-Inflamatórios não Esteroides/administração & dosagem , Anti-Inflamatórios não Esteroides/sangue , Anti-Hipertensivos/administração & dosagem , Anti-Hipertensivos/sangue , Pressão Sanguínea/efeitos dos fármacos , Adesão Celular/efeitos dos fármacos , Diclofenaco/administração & dosagem , Diclofenaco/sangue , Interações Medicamentosas , Edema/sangue , Edema/complicações , Edema/tratamento farmacológico , Citometria de Fluxo , Mucosa Gástrica/efeitos dos fármacos , Hipertensão/sangue , Hipertensão/complicações , Imuno-Histoquímica , Contagem de Leucócitos , Leucócitos/citologia , Leucócitos/efeitos dos fármacos , Losartan/administração & dosagem , Losartan/sangue , Masculino , Microcirculação/efeitos dos fármacos , Ratos , Ratos Endogâmicos SHR , Fator de Necrose Tumoral alfa/biossínteseRESUMO
A quantitative study of sodium diclofenac (Voltaren Emulgel, Novartis) phonophoresis was undertaken in humans. Fourteen healthy human volunteers were submitted to ultrasound irradiation on two 225-cm2 areas on the dorsum (group A), followed by the application of the medication gel, and the plasma diclofenac mass was measured at 1, 2 and 3 h later by high performance liquid chromatography. The same procedure was repeated one month later with the same volunteers but with the ultrasound equipment switched off for the control group (group B). The plasma diclofenac mass was significantly higher in group A than in group B at 1 h (0.0987 microg/mL as opposed to 0.0389 microg/mL; p=0.01) and 2 h (0.0724 microg/mL as opposed to 0.0529 microg/mL; p=0.01), but not at 3 h (0.0864 microg/mL as opposed to 0.0683 microg/mL; p=0.16). The authors conclude that previously applied therapeutic ultrasound irradiation enhances the percutaneous penetration of the topical diclofenac gel, although the mechanism remains unclear.
Assuntos
Anti-Inflamatórios não Esteroides/administração & dosagem , Diclofenaco/administração & dosagem , Fonoforese/métodos , Administração Tópica , Adulto , Anti-Inflamatórios não Esteroides/sangue , Anti-Inflamatórios não Esteroides/farmacocinética , Cromatografia Líquida de Alta Pressão/métodos , Diclofenaco/sangue , Diclofenaco/farmacocinética , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Absorção Cutânea/fisiologia , Terapia por Ultrassom/métodosRESUMO
The aim of the study was to assess the bioequivalence of two different diclofenac (CAS 15307-86-5) formulations (diclofenac free acid suspension as test formulation and diclofenac resinate suspension, Cataflam, as reference formulation) in 24 healthy volunteers. After an overnight fast, the volunteers received a single oral dose (50 mg) of each formulation, following an open, randomized, two-period crossover design, with a fourteen-day washout interval between doses. Serum samples were obtained over a 24-h interval post-dosing, and were analysed for their diclofenac content by HPLC-UV. No adverse effect was reported for any of the formulations administered. Geometric mean test/reference individual ratios were: 92.8% for AUC(0-24 h), 93.2% for AUC(0-infinity), 117.2% for Cmax, 131.0% for Ke and 76.2% for T1/2. The variability of Cmax parameter expressed as CV was greater than 25%. Since the 90% CI for AUC(0-24 h) mean ratio were within the 80-125% interval proposed by the Food and Drug Administration, it can be concluded that diclofenac free acid formulation is bioequivalent to diclofenac resinate formulation for the extent of absorption. Since the European Community Agency accepts a 90% CI for Cmax of 70-143%, it can be concluded that diclofenac free acid formulation is bioequivalent to diclofenac resinate formulation for both the rate and the extent of absorption after single dose administration.
Assuntos
Anti-Inflamatórios não Esteroides/farmacocinética , Diclofenaco/farmacocinética , Administração Oral , Adolescente , Adulto , Anti-Inflamatórios não Esteroides/administração & dosagem , Anti-Inflamatórios não Esteroides/sangue , Área Sob a Curva , Disponibilidade Biológica , Cromatografia Líquida de Alta Pressão , Estudos Cross-Over , Diclofenaco/administração & dosagem , Diclofenaco/sangue , Feminino , Humanos , Masculino , Espectrofotometria Ultravioleta , SuspensõesRESUMO
A rapid and sensitive method for the determination of diclofenac (CAS 15307-86-5) in whole blood samples by high-performance liquid chromatography with amperometric detection has been developed. This method was then used to study the pharmacokinetics of oral diclofenac sodium in the rat. The method includes a single extraction of acidified whole blood with ethyl acetate. Extracts were analyzed on a reversed-phase column eluted with a mixture of acetonitrile and 0.075 mol/l sodium acetate solution (pH 3.3) and detected amperometrically at + 1.1 V against Ag/AgCl. Retention times for diclofenac and the internal standard (naproxen) were 3.5 and 6 min, respectively. The method was linear in the range of 25 to 2000 ng/ml and the detection limit of the method was 10 ng/ml, using 100 microliters of whole blood sample. Employing this method, the oral pharmacokinetics of diclofenac in the rat was studied. Wistar male rats received an oral dose of 1, 3.2 or 10 mg/kg of diclofenac and blood samples were drawn at selected times during 12 h. After administration of diclofenac, a rapid increase of circulating concentrations was observed reaching a maximum in about 10 min. Then concentration decayed with a half-life of about 15 h. It is concluded that the method here reported is adequate for realization of pharmacokinetic studies of diclofenac in small species.
Assuntos
Anti-Inflamatórios não Esteroides/sangue , Diclofenaco/sangue , Animais , Anti-Inflamatórios não Esteroides/farmacocinética , Área Sob a Curva , Calibragem , Cromatografia Líquida de Alta Pressão , Diclofenaco/farmacocinética , Eletroquímica , Meia-Vida , Masculino , Naproxeno/sangue , Naproxeno/farmacocinética , Ratos , Ratos WistarRESUMO
The relationship between the pharmacokinetics and the antinociceptive effect of diclofenac was evaluated using the pain-induced functional impairment model in the rat. Male Wistar rats were injected with uric acid in the knee joint of the right hind limb, which induced its dysfunction. Once the dysfunction was complete, animals received a p.o. dose of 0.56, 1, 1.8, 3.2, 5.6 or 10 mg/kg of sodium diclofenac, and the antinociceptive effect and drug blood concentration were simultaneously evaluated at selected times for a period of 6 h. Diclofenac produced a dose-dependent antinociceptive effect, measured as a recovery of the functionality of the injured limb. However, the onset of the antinociceptive effect was delayed with respect to blood concentrations. Moreover, the effect lasted longer than expected from pharmacokinetic data. Therefore, when functionality index was plotted against diclofenac blood concentration, an anticlockwise hysteresis loop was observed for all doses. Hysteresis collapse was achieved using the effect-compartment model, and the plot of functionality index against diclofenac concentration in the effect-compartment data was well fitted by the sigmoidal Emax model. Our data suggest slow equilibrium kinetics between diclofenac concentration in blood and at its site of action, which leads to a delayed onset of the antinociceptive effect as well as a longer duration of the response resulting from drug accumulation in synovial fluid.
Assuntos
Anti-Inflamatórios não Esteroides/farmacologia , Diclofenaco/farmacologia , Animais , Anti-Inflamatórios não Esteroides/sangue , Anti-Inflamatórios não Esteroides/farmacocinética , Área Sob a Curva , Diclofenaco/sangue , Diclofenaco/farmacocinética , Masculino , Ratos , Ratos WistarRESUMO
The bioavailability of two suspension formulations of potassium diclofenac (Flogan, Merck and Cataflam, Ciba-Geigy) were compared in eighteen healthy male volunteers who received a single dose of 7 ml of each suspension (equivalent to 105 mg of potassium diclofenac) in an open randomized two period crossover design, with a fourteen-day washout period between doses. Serum samples were obtained over a 24 hour interval and diclofenac concentrations were determined by HPLC with ultraviolet detection. From the serum diclofenac concentration vs time curves, AUC[0-24] (area under the concentration vs time curves from 0-24 h), Cmax (maximum achieved concentration), Tmax (time to achieve Cmax) and Ke (terminal first order elimination constant) were obtained. Overlapping of Tmax intervals for both formulations was observed, but the important inter-subject variation observed in Cmax ratios did not allow equivalence conclusion for the rate of absorption. Equivalence in the extent of bioavailability between both potassium diclofenac suspension brands was concluded from the analysis of AUC[0-24] ratios.
Assuntos
Diclofenaco/farmacocinética , Adulto , Disponibilidade Biológica , Química Farmacêutica , Cromatografia Líquida de Alta Pressão , Diclofenaco/administração & dosagem , Diclofenaco/sangue , Humanos , Masculino , Pessoa de Meia-Idade , SuspensõesRESUMO
Diclofenac and nimesulide are non-steroidal antiinflammatory agents advocated for use in painful and inflammatory rheumatic and certain non rheumatic conditions. In Uruguay, these drugs are administered in doses of 100 mg and 200 mg once a day, respectively. Diclofenac is an effective and safe analgesic and antiinflammatory drug. There are scarce data available on the pharmacokinetic profile of nimesulide. These facts encouraged us to undertake the present study on clinical efficacy, tolerance and pharmacokinetics of nimesulide, controlled with sustained release diclofenac. Twenty patients with osteoarthritis, stage II-III, according to a clinical-radiological evaluation, were selected for the study. Patients were assigned at random to treatment A (Voltaren sustained release, 100 mg) or B (Nodo regular formulation, 200 mg) once a day. A double blind study with active drug and controlled parallel groups was designed. After a washout period of one week patients were treated with active medication during 84 days, and clinical controls every 14 days ensued. Experienced rheumatologists assessed pain and other clinical symptoms. Blood samples were drawn on days 7, 49 and 91 of the study, ten hours after the morning dose, and plasma diclofenac and nimesulide concentrations were measured. On day 7 and 91, blood counts and biochemical laboratory studies were performed (namely, hemoglobin, RBC, WBC, leucocyte differential count, platelet count, alkaline phosphatase, ASAT, ALAT, creatinine, etc.) Already two weeks after the study had begun, significant improvements in clinical parameters assessed were seen for both treatments. A trend to accumulation of diclofenac and nimesulide along the three months of treatment was observed.(ABSTRACT TRUNCATED AT 250 WORDS)
Assuntos
Diclofenaco/administração & dosagem , Artropatias/tratamento farmacológico , Articulação do Joelho , Sulfonamidas/administração & dosagem , Adulto , Idoso , Diclofenaco/sangue , Diclofenaco/farmacocinética , Método Duplo-Cego , Feminino , Seguimentos , Humanos , Artropatias/metabolismo , Masculino , Pessoa de Meia-Idade , Sulfonamidas/sangue , Sulfonamidas/farmacocinética , Fatores de TempoRESUMO
El diclofenac (liberación sostenida) y la nimesulida (fórmula convencional) son dos antiinflamatorios no esteroideos cuya dosificación es de un comprimido diario en nuestro país. Las escasas referencias en relación a la farmacocinética y duración de la acción de la nimesulida en pacientes añosos nos indujeron a diseñar el presente estudio controlado con diclofenac. Se selecionaron 20 pacientes con gonartrosis grado II-III asignándoles al azar el tratamiento A (diclofenac, liberación controlada 100mg) o B (nimesulida, presentación convencional 200mg). El estudio se desorrolló de acuerdo a un diseño doble ciego con grupos paralelos. Luego de un lavado de 7 días se comenzó con la medicación activa durante 84 días. Cada 14 días se evaluaron el dolor y otros parámetros clínicos. Se tomaron muestras de sangre los días 7, 49 y 91 a las 10 horas de la toma matutina para medir la concentración de los fármacos en plasma. Se realizaron exámenes de laboratório y al final del estudio. Ya a las dos semanas de comenzado el estudio se constataron mejorías estadísticamente significativas para los parámetros clínicos evaluados, que se mantuvieron durante todo el ensayo, en ambos tratamientos. El diclofenac y la nimesulida aumentaron su concentración plasmática durante los tres meses de estudio y se constató una aparente correlación lineal entre algunos parámetros clínicos y los niveles plasmáticos de los fármacos. La tolerancia, los exámenes de laboratório, y la apreciación clínica global del médico y del paciente para ambos grupos no mostraron diferencias estadísticamente significativas
Assuntos
Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Diclofenaco/administração & dosagem , Artropatias/tratamento farmacológico , Articulação do Joelho , Sulfonamidas/administração & dosagem , Diclofenaco/sangue , Diclofenaco/farmacocinética , Método Duplo-Cego , Seguimentos , Artropatias/metabolismo , Sulfonamidas/sangue , Sulfonamidas/farmacocinética , Fatores de TempoRESUMO
El diclofenac (liberación sostenida) y la nimesulida (fórmula convencional) son dos antiinflamatorios no esteroideos cuya dosificación es de un comprimido diario en nuestro país. Las escasas referencias en relación a la farmacocinética y duración de la acción de la nimesulida en pacientes añosos nos indujeron a diseñar el presente estudio controlado con diclofenac. Se selecionaron 20 pacientes con gonartrosis grado II-III asignándoles al azar el tratamiento A (diclofenac, liberación controlada 100mg) o B (nimesulida, presentación convencional 200mg). El estudio se desorrolló de acuerdo a un diseño doble ciego con grupos paralelos. Luego de un lavado de 7 días se comenzó con la medicación activa durante 84 días. Cada 14 días se evaluaron el dolor y otros parámetros clínicos. Se tomaron muestras de sangre los días 7, 49 y 91 a las 10 horas de la toma matutina para medir la concentración de los fármacos en plasma. Se realizaron exámenes de laboratório y al final del estudio. Ya a las dos semanas de comenzado el estudio se constataron mejorías estadísticamente significativas para los parámetros clínicos evaluados, que se mantuvieron durante todo el ensayo, en ambos tratamientos. El diclofenac y la nimesulida aumentaron su concentración plasmática durante los tres meses de estudio y se constató una aparente correlación lineal entre algunos parámetros clínicos y los niveles plasmáticos de los fármacos. La tolerancia, los exámenes de laboratório, y la apreciación clínica global del médico y del paciente para ambos grupos no mostraron diferencias estadísticamente significativas (AU)
Assuntos
Estudo Comparativo , Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Idoso , Diclofenaco/administração & dosagem , Sulfonamidas/administração & dosagem , Artropatias/tratamento farmacológico , Articulação do Joelho , Sulfonamidas/farmacocinética , Sulfonamidas/sangue , Diclofenaco/farmacocinética , Diclofenaco/sangue , Artropatias/metabolismo , Método Duplo-Cego , Seguimentos , Fatores de TempoRESUMO
A simple and sensitive micromethod based on HPLC is described for the measurement of diclofenac in 200 microliters plasma. A single extraction with dichloromethane in acidic medium was an essential clean-up step. Diclofenac and its internal standard (cyclohexendiphenyl propionic acid) was eluted at 3.3 and 6.5 min from a 4-micron C18 reverse-phase column using a mobile phase consisting of 0.75 M sodium acetate buffer, pH 5.0, and acetonitrile (55:45, v/v) at a flow rate of 0.9 ml/min with detection at 282 nm. The method, validated on the basis of parameters evaluated for the confidence limits of diclofenac measurements in spiked plasma, presented 1 ng/ml sensitivity, 10-10,000 ng/ml linearity, and 3.5% and 5.7% intra- and interassay precision, respectively. Peak plasma diclofenac levels ranging from 177 to 841 ng/ml and from 276 to 1008 ng/ml were obtained for two slow-release formulations. A wide range (1 ng/ml-3 micrograms/ml) was observed for plasma diclofenac levels of volunteers during a 24-h study period.