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1.
Respir Med ; 209: 107155, 2023 04.
Artículo en Inglés | MEDLINE | ID: mdl-36796547

RESUMEN

BACKGROUND: Hyperbaric oxygen therapy (HBOT) has been proposed to address COVID-19- associated respiratory failure. However, its biochemical effects are poorly known. METHOD: 50 patients with hypoxemic COVID-19 pneumonia were divided into C group (standard care) and H group (standard care plus HBOT). Blood was obtained at t = 0 and t = 5 days. Oxygen saturation (O2 Sat) was followed up. White blood cell (WC) count, lymphocytes (L) and platelets (P) and serum analysis (glucose, urea, creatinine, sodium, potassium, ferritin, D dimer, LDH and CRP) were carried out. Plasma levels of sVCAM, sICAM, sPselectin, SAA and MPO, and of cytokines (IL-1ß, IL-1RA, IL-6, TNFα, IFNα, IFNγ, IL-15, VEGF, MIP1α, IL-12p70, IL-2 and IP-10) were measured by multiplex assays. Angiotensin Converting Enzyme 2 (ACE-2) levels were determined by ELISA. RESULTS: The average basal O2 Sat was 85 ± 3%. The days needed to reach O2 Sat >90% were: H: 3 ± 1 and C: 5 ± 1 (P < 0,01). At term, H increased WC, L and P counts (all, H vs C: P < 0,01). Also, H diminished D dimer levels (H vs C, P < 0,001) and LDH concentration (H vs C, P < 0.01]. At term, H showed lower levels of sVCAM, sPselectin and SAA than C with respect to basal values (H vs C: ΔsVCAM: P < 0,01; ΔsPselectin: P < 0,05; ΔSAA: P < 0,01). Similarly, H showed diminished levels of TNFα (ΔTNFα: P < 0,05) and increased levels of IL-1RA and VEGF than C respect to basal values (H vs C: ΔIL-1RA and ΔVEGF: P < 0,05). CONCLUSION: Patients underwent HBOT improved O2 Sat with lower levels of severity markers (WC and platelets count, D dimer, LDH, SAA). Moreover, HBOT reduced proinflammatory agents (sVCAM, sPselectin, TNFα) and increased anti-inflammatory and pro-angiogenic ones (IL-1RA and VEGF).


Asunto(s)
COVID-19 , Oxigenoterapia Hiperbárica , Insuficiencia Respiratoria , Humanos , SARS-CoV-2 , COVID-19/complicaciones , COVID-19/terapia , Factor de Necrosis Tumoral alfa , Proteína Antagonista del Receptor de Interleucina 1 , Factor A de Crecimiento Endotelial Vascular , Insuficiencia Respiratoria/terapia
2.
Fundam Clin Pharmacol ; 37(3): 651-662, 2023 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-36639980

RESUMEN

Hemax® is an epoetin alfa product developed by Biosidus S.A. in Argentina at the end of the 1980s and has been present in that market since 1991. The initial presentation was a lyophilized powder containing albumin as stabilizer, to best adapt to environmental conditions in developing countries; more recently, a prefilled syringe, albumin-free presentation was developed, since this presentation has become the preferred standard in many markets. The primary objective was to compare the pharmacokinetic profile of different formulations of epoetin alfa after a single subcutaneous administration to healthy volunteers of 40 000 IU of Eprex/Erypo® and Hemax® PFS. This clinical trial was conceived following an open-label, randomized, three-way three-period cross-over balanced, and sequential design. The study was conducted on 24 healthy volunteers. To analyze similarity between Hemax® PFS and the innovator product, Eprex®, area under the curve (AUC) and Cmax of both products have been compared. The 90% CI lower limit for the geometric mean ratios was higher than 80% for any comparisons, and the 90% CI upper limit for these geometric ratios was below 125% for all the comparisons made, thus demonstrating equivalence between both products. The comparison between Hemax® PFS and Eprex® resulted in similar 90% CI for Cmax , AUC(0-120 h) and AUC(0-inf) ratios, all of them within the 80-125% interval, with a power above 95% for each ratio. These findings suggest biosimilar patterns for absorption velocity (with Tmax close to 15 h), absorption extent, and elimination (with an elimination half-life close to 25-30 h for each formulation).


Asunto(s)
Eritropoyetina , Humanos , Epoetina alfa/farmacocinética , Voluntarios Sanos , Área Bajo la Curva , Proteínas Recombinantes , Equivalencia Terapéutica , Inyecciones Subcutáneas
3.
Curr Drug Saf ; 11(2): 156-63, 2016.
Artículo en Inglés | MEDLINE | ID: mdl-27194037

RESUMEN

AIM: Renal transplant patients are frequently subject to polypharmacy and drug-drug interactions. However, no previous study has systematically assessed the risk of drug interactions and Adverse Drug Reactions (ADRs) in this population. METHODS: A total of 138 consecutive adult kidney transplant recipients admitted to our hospital between August 2010 and February 2012 were prospectively and systematically assessed by our pharmacovigilance team, within 24 hours of admission, to identify potential drug-drug interactions and probable ADRs. RESULTS: As a consequence of the high number of medications per patient (7.8±0.2 drugs), a considerable number of drugdrug interactions were observed in this population, with an average of 5.6±0.4 drug interactions per patient. Moreover, a significant percentage of admissions (~10%) of kidney transplant patients were related to probable ADRs. Almost all these patients had at least one drug interaction that could have potentially contributed to the probable ADR. Of note, clinically significant (i.e. severe) drug interactions were more frequent among patients with ADRs (29% vs. 15%, p<0.01). Also, patients with ADRs were more likely to have started a medication 30 days before admission (38.5% vs. 10.4%, p < 0.01). Non-immunosuppressive drugs most commonly involved in severe interactions were omeprazole, magnesium sulphate, and statins. The most commonly observed interactions were: tacrolimus and omeprazole, mycophenolate and omeprazole, sirolimus and enalapril, mycophenolate and antivirals, and mycophenolate and magnesium sulphate. CONCLUSION: Drug interactions were extremely frequent among kidney transplant recipients, and responsible for potentially avoidable ADRs. They should be carefully considered when following kidney transplant recipients.


Asunto(s)
Interacciones Farmacológicas/fisiología , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/diagnóstico , Trasplante de Riñón , Farmacovigilancia , Polifarmacia , Adulto , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/epidemiología , Femenino , Humanos , Inhibidores de Hidroximetilglutaril-CoA Reductasas/administración & dosificación , Inhibidores de Hidroximetilglutaril-CoA Reductasas/efectos adversos , Inmunosupresores/administración & dosificación , Inmunosupresores/efectos adversos , Trasplante de Riñón/tendencias , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Inhibidores de la Bomba de Protones/administración & dosificación , Inhibidores de la Bomba de Protones/efectos adversos
4.
Int J Clin Pharmacol Ther ; 54(10): 825-34, 2016 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-27049055

RESUMEN

OBJECTIVE: To evaluate the relative bioavailability of a new formulation of emtricitabine (EMT) 200 mg and tenofovir disoproxil fumarate (TNF) 300 mg and to compare with reference formulation to meet regulatory criteria in Argentina. METHODS: A randomized-sequence, open-label, twoperiod crossover study was conducted on 24 healthy Caucasian volunteers in a fasting state. A single oral dose of T or R formulations was followed by a 7-day washout period. Samples were collected at baseline, 0.25, 0.50, 0.75, 1, 1.25, 1.5, 2, 2.5, 3, 4, 7, 12, 24, and 48 hours after administration. EMT and TNF were determined by LC-MS/MS. RESULTS: Geometric means (90% CI) Cmax for EMT in test and reference were 1,891.22 (1,777.1 - 2,187.31) and 1,830.31 (1,721.19 - 2,134.01) ng/mL, the AUC0-t were 10,283.07 (9,624.29 - 11,566.34) and 10,518.76 (9,942.79 - 11,578.30) ng × h/mL and the AUC0-∞ were 10,615.14 (9,948.56 - 11,866.26) and 10,804.12 (10,221.04 - 11,864.85) ng × h/mL, respectively. For TNF test and reference, Cmax geometric means (CI range) were 202.91 (187.91 - 255.78) and 212.04 (195.98 - 264.87) ng/mL, AUC0-t were 1,429.96 (1,334.63 - 1,680.00) and 1,420.75 (1,326.76 - 1,622.18) ng × h/mL and AUC0-∞ were 1,657.11 (1,551.60 - 1,921.75) and 1,631.84 (1,523.95 - 1,857.97), respectively. No differences were detected between the formulations. The test/reference ratios (90% CI) for Cmax, AUC0-t, and AUC0-∞ were 103.33% (95.7 - 111.6), 97.76% (93.6 - 102.1), and 98.25% (94.3 - 102.4) for EMT, and 95.70% (85.9 - 106.6), 95.20% (83.4 - 108.6) and 91.10% (80.7 - 102.7) for TNF. CONCLUSIONS: In this single-dose study, the EMT/TNF tablets (test formulation) met the standard 90% CI criterion for bioequivalence with the reference formulation.


Asunto(s)
Fármacos Anti-VIH/administración & dosificación , Combinación Emtricitabina y Fumarato de Tenofovir Disoproxil/administración & dosificación , Adulto , Fármacos Anti-VIH/farmacocinética , Área Bajo la Curva , Argentina , Disponibilidad Biológica , Cromatografía Liquida , Estudios Cruzados , Combinación Emtricitabina y Fumarato de Tenofovir Disoproxil/farmacocinética , Femenino , Humanos , Masculino , Persona de Mediana Edad , Comprimidos , Espectrometría de Masas en Tándem , Equivalencia Terapéutica , Factores de Tiempo , Adulto Joven
5.
Int J Clin Pharmacol Ther ; 54(8): 649-56, 2016 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-27007999

RESUMEN

OBJECTIVE: To compare the pharmacokinetics, relative bioavailability (RB), immunogenicity, and safety after a single dose of test or reference formulation of teriparatide in healthy human volunteers in order to demonstrate whether both products are similar. RESEARCH DESIGN AND METHODS: We compared pharmacokinetic parameters, immunogenicity, and safety after a single dose of two formulations (Osteofortil® and Forteo®) of teriparatide in a randomizedsequence, open-label, two-period crossover study in 24 healthy volunteers. The washout period between formulations was 7 days. Blood samples were collected at baseline and 0, 5, 10, 15, 20, 25, 30, 45, 60, 75, 90, 120, 150 minutes, and 3 and 4 hours after administration. Teriparatide concentrations were determined using ELISA. Adverse events were monitored. RESULTS: Geometric mean (90% CI) Cmax for test and reference formulations were 165.86 (153.35 - 212.13) and 175.37 (164.04 - 221.04) pg/mL, the AUC0-t was 14,932 (5,275 - 15,752) and 14,153 (1,861 - 16,875) pg×min/mL, and the AUC0-∞ was 16,147 (15,047 - 18,799) and 15,467 (14,473 - 18,126) pg×min/mL, respectively. The test/reference ratios (90% CI) for Cmax, AUC0-t, and AUC0-∞ were 94.58% (85.29 - 104.87), 105.5% (97.77 - 113.84), and 104.4% (96.97 - 112.39), respectively No subject reported adverse events. CONCLUSION: Test formulation met pharmacokinetic criteria for bioequivalence.


Asunto(s)
Conservadores de la Densidad Ósea/farmacocinética , Teriparatido/farmacocinética , Adulto , Disponibilidad Biológica , Química Farmacéutica , Estudios Cruzados , Femenino , Voluntarios Sanos , Humanos , Masculino , Persona de Mediana Edad , Teriparatido/efectos adversos , Equivalencia Terapéutica
6.
Curr Drug Saf ; 11(3): 206-14, 2016.
Artículo en Inglés | MEDLINE | ID: mdl-26916784

RESUMEN

UNLABELLED: In recent years, several cases of torsade de pointes have been associated with many opioids. However, to present no cases have been reported with tramadol. OBJECTIVE: To evaluate the effect of tramadol on QT-interval in the clinical setting. RESEARCH DESIGN AND METHODS: Medical history and comorbidities predisposing to QT interval prolongation were registered for patients requiring medical assistance that involved tramadol administration. Ionograms and ECGs were performed at baseline and intratreatment; QT interval was analyzed after correction with Bazzet, Fridericia, Framinghan and Hogdes formula. RESULTS: 115 patients were studied (50.4% males) All patients had received tramadol 150-400 mg/day during 3.0-5.0 days at the moment of intratreatment control. Plasma concentrations of tramadol were 201-1613 ng/mL. Intratreatment electrocardiographic control, as mean ± SD (range), showed QTcB 372±32 (305 to 433), QTcFri 356±37 (281 to 429), QTcFra 363±33 (299 to 429), QTcH 362±30 (304 to 427), ΔQTcB 26±40 (-73 to 110), ΔQTcFri 24±48 (-97 to 121), ΔQTcFra 22±42 (-81 to 109) and .QTcH 22±38 (-68 to 110) ms. QTc interval presents high correlation with plasma tramadol concentrations (for .QTc, R>0.77). Renal failure was associated with a relative risk for ΔQTc > 30 ms of 1.90 (IC95% 1.31-2.74) and for ΔQTc > 60 ms of 4.74 (IC95% 2.57-8.74). No patient had evidence of arrhythmia during the present study. CONCLUSION: Tramadol produces QTc interval prolongation in good correlation with plasma drug concentrations; renal failure is a risk factor for higher concentration and QT prolongation by tramadol.


Asunto(s)
Analgésicos Opioides/efectos adversos , Analgésicos Opioides/sangre , Síndrome de QT Prolongado/sangre , Síndrome de QT Prolongado/inducido químicamente , Tramadol/efectos adversos , Tramadol/sangre , Anciano , Anciano de 80 o más Años , Argentina/epidemiología , Estudios de Cohortes , Electrocardiografía/efectos de los fármacos , Femenino , Humanos , Síndrome de QT Prolongado/epidemiología , Estudios Longitudinales , Masculino , Persona de Mediana Edad , Prevalencia , Estudios Prospectivos
7.
Curr Drug Saf ; 11(1): 86-98, 2016.
Artículo en Inglés | MEDLINE | ID: mdl-26537523

RESUMEN

OBJECTIVE: The actual prevalence of drug induced QTc prolongation in clinical practice is unknown. Our objective was to determine the occurrence and characteristics of drug-induced QT prolongation in several common clinical practices. Additionally, a subgroup of patients treated with dextropropoxyphene of particular interest for the regulatory authority was analysed. RESEARCH DESIGN AND METHODS: Medical history and comorbidities predisposing to QT interval prolongation were registered for 1270 patient requiring medical assistance that involved drug administration. Three ionograms and ECGs were performed: baseline, intra- and after treatment; QT interval was corrected with Bazzet formula. RESULTS: Among patients, 9.9% presented QTc >450/470 ms, 3% QTc > 500 ms, 12.7% ΔQTc >30 ms and 5.2% ΔQTc >60 ms. QTc prolongation associated with congestive heart failure, ischemic cardiopathy, diabetes, renal failure, arrhythmias, hypothyroidism, and bradycardia. At univariate analysis, clarithromycin, haloperidol, tramadol, amiodarone, glyceryl trinitrate, amoxicillin + clavulanic acid, amoxicillin + sulbactam, ampicillin + sulbactam, fentanyl, piperacillin + tazobactam, and diazepam prolonged QTc. Prolongation remained significantly associated with furosemide, clarithromycin, glyceryl trinitrate and betalactamase inhibitors after multivariate analysis. CONCLUSION: QT interval prolongation in everyday practice is frequent, in association to clinical factors and drugs that can be easily identified for monitoring and prevention strategies.


Asunto(s)
Electrocardiografía/efectos de los fármacos , Síndrome de QT Prolongado/inducido químicamente , Síndrome de QT Prolongado/diagnóstico , Adulto , Anciano , Antibacterianos/efectos adversos , Dextropropoxifeno/efectos adversos , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/diagnóstico , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/epidemiología , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/etiología , Electrocardiografía/métodos , Femenino , Humanos , Síndrome de QT Prolongado/fisiopatología , Estudios Longitudinales , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Factores de Riesgo
8.
Int J Risk Saf Med ; 25(3): 185-92, 2013.
Artículo en Inglés | MEDLINE | ID: mdl-24047689

RESUMEN

BACKGROUND: Adverse Drug Reactions (ADR) are a major cause of morbidity and mortality worldwide. In spite of this, ADR are largely underreported and unrecognized. PURPOSE: Identify and characterize ADR related admissions to our internal medicine ward using a proactive multidisciplinary pharmacovigilance approach. METHODS: Within 24 hrs of admission 1045 patients admitted to the Internal Medicine Ward between August 2010 and February 2012 were screened for possible or probable ADR related admissions. RESULTS: Probable ADR accounted for 112 of 1045 admissions (10.7%, 95% Confidence Interval [CI]: 8.8-12.6%), of which only 16 (14.3%) were classified as unavoidable. NSAIDs were the drug group more commonly implicated in probable ADR-related admissions (17.0%), followed by antiplatelets (16.1%). In-hospital mortality of patients admitted due to probable ADR was 8.0% (95% CI: 2.9-13.1%). During this study period, 6% of internal medicine ward and 4% of critical care unit beds were occupied by patients with probable ADR. The estimated cost of care of these patients was 641,000 US dollars (USD). CONCLUSION: ADR are a frequent reason for admission to an Internal Medicine Ward in Argentina. The culprit drugs and interactions are similar to those reported in the literature. The cost is substantial and most of the ADR are potentially avoidable.


Asunto(s)
Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/epidemiología , Hospitalización/estadística & datos numéricos , Anciano , Argentina/epidemiología , Femenino , Humanos , Tiempo de Internación/estadística & datos numéricos , Masculino
9.
Clin Ther ; 33(4): 500-10, 2011 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-21635995

RESUMEN

BACKGROUND: Currently, levodopa administered with decarboxylase inhibitors is the gold standard for the management of the motor symptoms of Parkinson's disease, a neurodegenerative disorder characterized by the degeneration of dopaminergic neurons in the substantia nigra pars compacta. In Argentina, only 1 commercial product is available with such composition; this study was contracted by the manufacturer to comply with new generic product regulations. OBJECTIVE: The aim of this study was to evaluate the fasting bioavailability of a new generic formulation of levodopa 200 mg/benserazide 50 mg tablets (test) and compare this generic formulation with the branded formulation (reference) to meet regulatory criteria for marketing the test product in Argentina. METHODS: A randomized-sequence, open-label, 2-period, crossover study was conducted between August and October 2009 in healthy Caucasian volunteers (n = 24; 18 males, aged 21 to 42 years, with a body mass index ranging from 19.7 to 26.0 kg/m(2)) in the fasted state. A single oral dose of the test or reference formulation was administered, and after a 7-day washout period, the other formulation was given. Blood samples were collected at baseline and at 10, 20, 30, 40, 50, 60, 70, 80, 90, and 105 minutes and 2, 2.5, 3, 3.5, 4, and 6 hours after dosing. Levodopa plasma concentrations were measured by high-performance liquid chromatography with electrochemical detection, without stereo-specificity assessment. The formulations were considered bioequivalent if the 90% CI of the geometric mean ratios (test/reference) for the C(max) and AUC(0-t) of levodopa were within the 0.8 to 1.25 range. Adverse events were monitored throughout the study, based on clinical parameters and patient reports. RESULTS: The geometric means (90% CI) of the C(max) for the test and reference formulations were 2462.02 (2312.06-3492.40) and 2542.85 (2394.49-3231.29) ng/mL, respectively; the AUC(0-t) was 3878.04 (3623.88-5393.09) and 3972.10 (3765.88-5393.02) ng/mL/h, respectively; and the AUC(0-∞)was 4610.37 (4315.71-6315.70) and 4728.96 (4502.17-6828.26) ng/mL/h, respectively. There were no significant differences in pharmacokinetic parameters between the 2 formulations. The test:reference ratios for C(max), AUC(0-t), and AUC(0-∞) were 96.82% (90% CI, 83.87-111.77), 97.63% (90% CI, 85.95-110.91), and 97.49% (90% CI, 84.09-113.02), respectively. No clinically significant adverse events were reported; this finding is probably the result of subjects not believing that their side effects were severe enough to be reported and not because of a genuine and absolute lack of predictable side effects. CONCLUSIONS: In this single-dose study, the test formulation of levodopa/benserazide tablets met the Argentinean criterion for bioequivalence to the reference formulation. (www.clinicaltrials.gov: NCT01327261).


Asunto(s)
Antiparkinsonianos/farmacocinética , Benserazida/farmacocinética , Medicamentos Genéricos/farmacocinética , Levodopa/farmacocinética , Administración Oral , Adulto , Antiparkinsonianos/administración & dosificación , Antiparkinsonianos/efectos adversos , Área Bajo la Curva , Argentina , Benserazida/administración & dosificación , Benserazida/efectos adversos , Disponibilidad Biológica , Cromatografía Líquida de Alta Presión , Estudios Cruzados , Combinación de Medicamentos , Medicamentos Genéricos/administración & dosificación , Medicamentos Genéricos/efectos adversos , Femenino , Humanos , Levodopa/administración & dosificación , Levodopa/efectos adversos , Masculino , Comprimidos , Equivalencia Terapéutica , Adulto Joven
10.
Clin Ther ; 32(1): 161-70, 2010 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-20171421

RESUMEN

BACKGROUND: Platelet activation is a major component in the pathogenesis of coronary thrombosis and myocardial infarction. Thienopyridines, particularly clopidogrel, are highly effective in reducing in-stent thrombosis and functional inhibition of adenosine diphosphate-induced platelet activation. OBJECTIVE: The aim of this study was to evaluate the bioequivalence of a new generic formulation of clopidogrel 75-mg tablets (test) and the available branded formulation (reference) to meet regulatory criteria for marketing the test product in Argentina. METHODS: This was a randomized-sequence, open-label, 2-period crossover study conducted in healthy white volunteers in the fasted state. A single oral dose of the test or reference formulation was followed by a 7-day washout period, after which subjects received the alternative formulation. Blood samples were collected at baseline and at 0.25, 0.5, 0.75, 1, 1.25, 1.5, 2, 2.5, 3, 4, 6, 8, and 12 hours after dosing. Clopidogrel concentrations were determined using an LC-MS/MS method. The formulations were considered bioequivalent if the 90% CI of the geometric mean ratios (test:reference) for C(max) and AUC(0-last) were within the range from 80% to 125%. Adverse events were monitored throughout the study based on clinical parameters and patient reports. RESULTS: Twenty-four volunteers (13 male, 11 female; mean [SD] age, 33.7 [5.2] years [range, 21-42 years]; weight, 72.4 [6.83] kg [range, 59-82 kg]) were enrolled in and completed the study. The geometric mean C(max) for the test and reference formulations was 877.76 and 913.49 pg/mL, respectively. The geometric mean AUC(0-t) was 1911.53 and 2053.09 pg . h/mL, and the geometric mean AUC(0-infinity)) was 2021.33 and 2188.25 pg . h/mL. The geometric mean ratios (test:reference) for C(max), AUC(0-t), and AUC(0-infinity)) were 96.09% (90% CI, 90.71-101.78), 93.10% (90% CI, 85.57-101.3), and 92.37% (90% CI, 85.06-100.31), respectively. There were no significant differences in pharmacokinetic parameters between groups. No adverse events were reported. CONCLUSION: In this single-dose study in healthy fasted volunteers, the test formulation of clopidogrel tablets met the US and Argentinian regulatory criterion for bioequivalence to the reference formulation.


Asunto(s)
Medicamentos Genéricos/farmacocinética , Inhibidores de Agregación Plaquetaria/sangre , Inhibidores de Agregación Plaquetaria/farmacocinética , Ticlopidina/análogos & derivados , Administración Oral , Adulto , Área Bajo la Curva , Argentina , Cromatografía Líquida de Alta Presión , Clopidogrel , Estudios Cruzados , Medicamentos Genéricos/administración & dosificación , Femenino , Humanos , Masculino , Inhibidores de Agregación Plaquetaria/administración & dosificación , Valores de Referencia , Comprimidos , Espectrometría de Masas en Tándem , Equivalencia Terapéutica , Ticlopidina/administración & dosificación , Ticlopidina/sangre , Ticlopidina/farmacocinética , Adulto Joven
11.
Clin Ther ; 30(11): 2015-23, 2008 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-19108789

RESUMEN

BACKGROUND: Levothyroxine has a narrow therapeutic index; therefore, precise and accurate assessment of the bioequivalence of different levothyroxine products is critical. Bioavailability estimates of levothyroxine formulations might be affected by baseline concentrations of the hormone. OBJECTIVES: The aim of this study was to assess the bioequivalence of 100 microg of a test (T4 Montpellier 100, Química Montpellier S.A., Buenos Aires, Argentina) and reference (Synthroid, Abbott Laboratories, Abbott Park, Illinois) formulation of levothyroxine. We also compared 2 methods of levothyroxine measurements: without and with baseline correction for endogenous levothyroxine. METHODS: This randomized, open-label, 2-sequence, crossover study with a 65-day washout period was carried out in healthy, white, euthyroid volunteers following a single dose of sodium levothyroxine 600 microg. Blood samples were collected at 30 and 15 minutes prior to administration, and 0 (baseline), 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 24, and 48 hours to determine thyroxine; serum thyrotropin (TSH) concentrations were determined 30 minutes before administration and 48 hours after administration. Serum concentrations of thyroxine were determined through radioimmunoassay and serum TSH concentrations were determined by a validated 2-site immunoradiometric assay. The formulations are considered to be equivalent if the 90% CI ratios for C(max) and AUC(0-last) are within 80% to 125%, per the US Food and Drug Administration (FDA). Adverse event monitoring was performed throughout the study by assessing clinical parameters (eg, blood pressure, electrocardiogram) and patient reports. RESULTS: A total of 24 volunteers (16 male, 8 female; mean [SD] age, 30.2 [4.6] years [range, 21-40 years]; mean [SD] weight, 71.71 [7.52] kg [range, 58-83 kg]) were included in the study. Without adjustment for baseline levels of endogenous levothyroxine, geometric mean C(max) for the test and reference formulations were 8.92 and 9.39 microg/dL, respectively; AUC(0-last) values were 368.40 and 383.37 microg/mL . h(-1). The 90% CI of the geometric mean for the percent ratios (test: reference) of C(max) and AUC(0-last) were 95.1% (90% CI, 91.9-98.3) and 96.1% (90% CI, 94.0-98.2), respectively. With adjustment for baseline levels of endogenous levothyroxine, the geometric mean C(max) for the test and reference formulations were 3.16 and 3.39 microg/dL, respectively; AUC(0-last) values were 88.33 and 95.60 microg/mL . h(-1). Despite performing the adjustment, the 90% CI of the geometric mean for Cmax and AUC(0-last) test:reference ratios were 93.1% (90% CI, 84.9-102.2) and 92.4% (90% CI, 85.2-100.2), respectively. No significant between-group differences were found with regard to pharmacokinetic parameters. No adverse events were observed or reported. CONCLUSION: The results of this study suggest that the test formulation was bioequivalent to the reference formulation of levothyroxine in these healthy volunteers, according to the US FDA definition of bioequivalence. This was supported by the analysis of concentration-time profiles without and with correction for basal endogenous levothyroxine.


Asunto(s)
Tiroxina/sangre , Tiroxina/farmacocinética , Administración Oral , Adulto , Análisis de Varianza , Área Bajo la Curva , Argentina , Estudios Cruzados , Femenino , Humanos , Masculino , Matemática , Tasa de Depuración Metabólica , Comprimidos , Equivalencia Terapéutica , Tiroxina/administración & dosificación , Factores de Tiempo , Adulto Joven
12.
Medicina (B Aires) ; 66(2): 150-2, 2006.
Artículo en Español | MEDLINE | ID: mdl-16715766

RESUMEN

Abdominal distention is a frequent symptom, being often the initial presentation of systemic diseases or gastrointestinal disorders. Other causes are uncommon. Spermatic cord cysts are infrequent, abdominal location is even rarer, and the size of the cysts is usually not enough to produce abdominal distention. In our case a man with bilateral cryptorchidism was admitted with abdominal distention and edema of the lower extremities initially interpreted as asciticedematous syndrome. Ultrasonography interpreted abdominal distention as septate ascites, computed tomography as a giant cyst. Exploratory surgery showed a giant spermatic cord cyst in the left spermatic cord.


Asunto(s)
Edema/etiología , Quiste Epidérmico/complicaciones , Enfermedades de los Genitales Masculinos/complicaciones , Obstrucción Intestinal/etiología , Cordón Espermático , Adolescente , Criptorquidismo/complicaciones , Diagnóstico Diferencial , Dilatación Patológica/patología , Quiste Epidérmico/patología , Enfermedades de los Genitales Masculinos/patología , Humanos , Obstrucción Intestinal/patología , Masculino , Cordón Espermático/patología
13.
Medicina (B.Aires) ; 66(2): 150-152, 2006. ilus
Artículo en Español | LILACS | ID: lil-440405

RESUMEN

La distensión abdominal es un síntoma común, siendo en general la presentación inicial de enfermedadessistémicas o desórdenes gastrointestinales. Otras causas son infrecuentes. Los quistesdel cordón espermático son poco frecuentes, pero aún más su ubicación intraabdominal, su tamaño habitual esinsuficiente para producir distensión. El paciente presentado en este caso es un varón con criptorquidia bilateraladmitido por distensión abdominal, interpretada inicialmente como síndrome ascítico edematoso. La ecografíainterpretó la distensión como ascitis tabicada, y la tomografía computada como debida a un gran quiste. En laexploración quirúrgica se diagnosticó un quiste gigante del cordón espermático de ubicación abdominal.


Abdominal distention is a frequentsymptom, being often the initial presentation of systemic diseases or gastrointestinal disorders. Othercauses are uncommon. Spermatic cord cysts are infrequent, abdominal location is even rarer, and the size ofthe cysts is usually not enough to produce abdominal distention. In our case a man with bilateral cryptorchidismwas admitted with abdominal distention and edema of the lower extremities initially interpreted as asciticedematoussyndrome. Ultrasonography interpreted abdominal distention as septate ascites, computed tomographyas a giant cyst. Exploratory surgery showed a giant spermatic cord cyst in the left spermatic cord.


Asunto(s)
Humanos , Masculino , Adolescente , Edema/etiología , Quiste Epidérmico/patología , Obstrucción Intestinal/etiología , Cordón Espermático/patología , Diagnóstico Diferencial , Dilatación Patológica , Quiste Epidérmico/complicaciones , Enfermedades de los Genitales Masculinos/patología , Obstrucción Intestinal/patología
14.
Medicina (B.Aires) ; 66(2): 150-152, 2006. ilus
Artículo en Español | BINACIS | ID: bin-123444

RESUMEN

La distensión abdominal es un síntoma común, siendo en general la presentación inicial de enfermedadessistémicas o desórdenes gastrointestinales. Otras causas son infrecuentes. Los quistesdel cordón espermático son poco frecuentes, pero aún más su ubicación intraabdominal, su tamaño habitual esinsuficiente para producir distensión. El paciente presentado en este caso es un varón con criptorquidia bilateraladmitido por distensión abdominal, interpretada inicialmente como síndrome ascítico edematoso. La ecografíainterpretó la distensión como ascitis tabicada, y la tomografía computada como debida a un gran quiste. En laexploración quirúrgica se diagnosticó un quiste gigante del cordón espermático de ubicación abdominal. (AU)


Abdominal distention is a frequentsymptom, being often the initial presentation of systemic diseases or gastrointestinal disorders. Othercauses are uncommon. Spermatic cord cysts are infrequent, abdominal location is even rarer, and the size ofthe cysts is usually not enough to produce abdominal distention. In our case a man with bilateral cryptorchidismwas admitted with abdominal distention and edema of the lower extremities initially interpreted as asciticedematoussyndrome. Ultrasonography interpreted abdominal distention as septate ascites, computed tomographyas a giant cyst. Exploratory surgery showed a giant spermatic cord cyst in the left spermatic cord. (AU)


Asunto(s)
Humanos , Masculino , Adolescente , Quiste Epidérmico/patología , Cordón Espermático/patología , Edema/etiología , Obstrucción Intestinal/etiología , Dilatación Patológica , Quiste Epidérmico/complicaciones , Obstrucción Intestinal/patología , Enfermedades de los Genitales Masculinos/patología , Diagnóstico Diferencial
15.
Medicina (B.Aires) ; 66(2): 150-152, 2006. ilus
Artículo en Español | BINACIS | ID: bin-119577

RESUMEN

La distensión abdominal es un síntoma común, siendo en general la presentación inicial de enfermedadessistémicas o desórdenes gastrointestinales. Otras causas son infrecuentes. Los quistesdel cordón espermático son poco frecuentes, pero aún más su ubicación intraabdominal, su tamaño habitual esinsuficiente para producir distensión. El paciente presentado en este caso es un varón con criptorquidia bilateraladmitido por distensión abdominal, interpretada inicialmente como síndrome ascítico edematoso. La ecografíainterpretó la distensión como ascitis tabicada, y la tomografía computada como debida a un gran quiste. En laexploración quirúrgica se diagnosticó un quiste gigante del cordón espermático de ubicación abdominal. (AU)


Abdominal distention is a frequentsymptom, being often the initial presentation of systemic diseases or gastrointestinal disorders. Othercauses are uncommon. Spermatic cord cysts are infrequent, abdominal location is even rarer, and the size ofthe cysts is usually not enough to produce abdominal distention. In our case a man with bilateral cryptorchidismwas admitted with abdominal distention and edema of the lower extremities initially interpreted as asciticedematoussyndrome. Ultrasonography interpreted abdominal distention as septate ascites, computed tomographyas a giant cyst. Exploratory surgery showed a giant spermatic cord cyst in the left spermatic cord. (AU)


Asunto(s)
Humanos , Masculino , Adolescente , Quiste Epidérmico/patología , Cordón Espermático/patología , Edema/etiología , Obstrucción Intestinal/etiología , Dilatación Patológica , Quiste Epidérmico/complicaciones , Obstrucción Intestinal/patología , Enfermedades de los Genitales Masculinos/patología , Diagnóstico Diferencial
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