RESUMEN
PURPOSE: To describe the clinical manifestation and the treatment of complex regional pain syndrome type II in childhood. METHODS: Using information on the symptoms, diagnosis, rehabilitation and outcome of a young patient with complex regional pain syndrome type II. RESULTS: A 9-year -old girl had severe pain in the region of the left foot, signs of a common fibular nerve entrapment, hyperalgesia not limited to the distribution of the injured nerve, weakness and temperature asymmetry unknown origin. She consulted few doctor's before she was given the right diagnosis of complex regional pain syndrome type II. Following the diagnosis the treatment started, it included intensive physiotherapy, electrical therapy and also supportive psychological therapy. Half a year later, the patient was free of the daily pain and returned to all physical activity without any restrictions. CONCLUSIONS: The case report illustrates that peripheral nerve compression or injuries specifically, complex regional pain syndrome type II, should be taken into consideration when evaluating children with weakness and pain of the lower or upper limb. Implication of rehabilitation Raising the awareness of complex regional pain syndrome in the childhood is essential for an early diagnosis and appropriate treatment. The treatment options include early and adequate pain management inclusive electrical therapy and physiotherapy. Psychological therapy helps to avoid psychological stress reaction and the disease negative impact on the child's education and sports and the family social life.
Asunto(s)
Síndromes de Dolor Regional Complejo , Terapia por Estimulación Eléctrica/métodos , Pie , Modalidades de Fisioterapia , Técnicas Psicológicas , Niño , Síndromes de Dolor Regional Complejo/diagnóstico , Síndromes de Dolor Regional Complejo/fisiopatología , Síndromes de Dolor Regional Complejo/psicología , Síndromes de Dolor Regional Complejo/rehabilitación , Ejercicio Físico , Femenino , Pie/inervación , Pie/fisiopatología , Humanos , Hiperalgesia/diagnóstico , Hiperalgesia/etiología , Hiperalgesia/terapia , Síndromes de Compresión Nerviosa/diagnóstico , Síndromes de Compresión Nerviosa/fisiopatología , Síndromes de Compresión Nerviosa/terapia , Dimensión del Dolor/métodos , Resultado del TratamientoRESUMEN
BACKGROUND: In vitro studies suggest that antimicrobial activity of antibiotics meant to treat central nervous system infections such as meningitis or ventriculitis may be altered by cerebrospinal fluid (CSF). This could explain the reason behind the often observed discrepancies between the activity of antibiotics determined in artificial growth media in vitro, and their sometimes reduced clinical efficacy in CSF in vivo. If conducted in CSF, in vitro microbiological investigations might predict the ability of antibiotic drugs to treat CSF infections better than experiments in artificial growth media. In addition, they are less expensive, critical and time consuming than animal studies, and might potentially be appreciated in drug development as a rapid and cost-effective means to gain valuable information on drugs meant to treat infections residing in CSF. SUMMARY: Data from microbiological in vitro experiments performed in CSF were compiled for fosfomycin, rifampicin, cefepime, cefotaxime, ceftriaxone, ciprofloxacin, gentamicin and vancomycin. Where possible, correlations between in vitro data and evidence from in vivo studies were established. KEY MESSAGES: As discussed in the text, no clear correlations between in vitro studies in CSF and clinical outcomes could be identified. Methodological recommendations derived from the collected studies are summarized in order to optimize future research on the topic.
Asunto(s)
Antibacterianos/farmacología , Líquido Cefalorraquídeo/microbiología , Animales , Antibacterianos/uso terapéutico , Bacterias/efectos de los fármacos , Infecciones Bacterianas/tratamiento farmacológico , Líquido Cefalorraquídeo/química , Líquido Cefalorraquídeo/citología , HumanosRESUMEN
PURPOSE: The present open single-centre, descriptive and comparative pharmacokinetic study aimed to investigate the efficacy of iontophoresis to enhance transdermal delivery by measuring concentration vs. time profiles of diclofenac in local tissue and in plasma in two separate study periods. METHODS: Period 1 determined diclofenac concentrations in both calf muscles simultaneously by using microdialysis after applying diclofenac gel topically as a single dose of 5 g with or without iontophoresis in eight healthy volunteers. In period 2, the same dose was applied to another 8 volunteers to determine plasma concentrations of diclofenac either with or without iontophoresis in a cross over design. RESULTS: In period 1, tissue concentrations were found to be under the limit of detection of 0.5 ng/ml both with and without iontophoresis in all subjects. In period 2, after iontophoresis in 75% of study participants, plasma concentrations of diclofenac could be determined, but only in 25% without iontophoresis. Although area under the concentration-time-curve (AUC, 187.97 ± 315.92 vs. 22.92 ± 42.44 ng*min/ml) and maximum concentration (Cmax, 2.06 ± 3.79 vs. 0.22 ± 0.41 ng/ml) values showed a numerically clear trend for higher values with iontophoresis compared to passive diffusion, no significant difference could be found due to high inter-individual variability. In total, 18.75% of all subjects presented adverse events. CONCLUSIONS: Despite a higher percentage of subjects showed detectable plasma levels of diclofenac after iontophoresis, iontophoresis failed to achieve potentially more effective topical concentrations. The typical mechanism of iontophoresis like electromigration, electroosmosis and increased subcutaneous circulation could be responsible for the results of the present observation. Additional clinical studies are needed to justify the transdermal delivery of diclofenac by using iontophoresis.
Asunto(s)
Antiinflamatorios no Esteroideos/administración & dosificación , Antiinflamatorios no Esteroideos/farmacocinética , Diclofenaco/administración & dosificación , Diclofenaco/farmacocinética , Iontoforesis , Músculo Esquelético/metabolismo , Administración Tópica , Antiinflamatorios no Esteroideos/sangre , Diclofenaco/sangre , Voluntarios Sanos , Humanos , MasculinoRESUMEN
The underlying pathology of diabetic wounds, i.e. impairment of macro- and microcirculation, might also impact target site penetration of antibacterial drugs. To compare tissue concentrations of linezolid in infected and not infected tissue 10 patients suffering from type 2 diabetes with foot infection were included in the study. Tissue penetration of linezolid was assessed using in vivo microdialysis at the site of infection as well as in non-inflamed subcutaneous adipose tissue. All patients were investigated after receiving a single dose of linezolid and five patients in addition at steady state. After a single dose of linezolid significantly higher area under the concentration vs. time curve over 8 hours (AUC0-8 ) and maximum concentrations (Cmax )-values were observed in plasma (65.5 ± 21.2 mg*h/L and 16.4 ± 4.6 mg/L) as compared to inflamed (36.3 ± 22.9 mg*h/L and 6.6 ± 3.6 mg/L) and non-inflamed tissue (33.0 ± 17.7 mg*h/L and 6.7 ± 3.6 mg/L). Multiple administrations of linezolid led to disappearance of significant differences in Cmax and AUC0-8 between plasma, inflamed, and non-inflamed tissue. Approximately 2-fold increase of Cmax and AUC0-8 -values in tissue was observed at steady state as compared to the first administration. Penetration of linezolid is not impaired in diabetic foot infection but equilibrium between plasma and tissue might be delayed.
Asunto(s)
Acetamidas/farmacocinética , Antiinfecciosos/farmacocinética , Diabetes Mellitus Tipo 2/metabolismo , Enfermedades del Pie/metabolismo , Oxazolidinonas/farmacocinética , Infecciones de los Tejidos Blandos/metabolismo , Acetamidas/administración & dosificación , Acetamidas/sangre , Anciano , Anciano de 80 o más Años , Antiinfecciosos/administración & dosificación , Antiinfecciosos/sangre , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Femenino , Enfermedades del Pie/tratamiento farmacológico , Humanos , Linezolid , Masculino , Microdiálisis , Persona de Mediana Edad , Oxazolidinonas/administración & dosificación , Oxazolidinonas/sangre , Infecciones de los Tejidos Blandos/tratamiento farmacológicoRESUMEN
AIM: Muscle injuries and extensive exercise are associated with cyclo-oxygenase dependent formation of inflammatory prostaglandins. Since the effect of topical administration of non-steroidal anti-inflammatory drugs (NSAIDs) on local cyclo-oxygenase is unknown, the present exploratory, open label, non-randomized study set out to measure exercise induced release of prostaglandins before and after epicutaneous administration of diclofenac. METHODS: Microdialysis was used to determine the local interstitial concentration of PGE2 and 8-iso-PGF2α as well as diclofenac concentrations in the vastus lateralis under rest, dynamic exercise and during recovery in 12 healthy subjects at baseline and after a treatment phase applying a total of seven plasters medicated with 180 mg of diclofenac epolamine over 4 days. RESULTS: At baseline PGE2 concentrations were 1169 ± 780 pg ml(-1) at rest and 1287 ± 459 pg ml(-1) during dynamic exercise and increased to 2005 ± 1126 pg ml(-1) during recovery. After treatment average PGE2 concentrations were 997 ± 588 pg ml(-1) at rest and 1339 ± 892 pg ml(-1) during exercise. In contrast with the baseline phase no increase in PGE2 concentrations was recorded during the recovery period after treatment (PGE2 1134 ± 874 pg ml(-1)). 8-iso-PGF2α was neither affected by exercise nor by treatment with diclofenac. Local and systemic concentrations of diclofenac were highly variable but comparable with previous clinical pharmacokinetic studies. CONCLUSIONS: We can hypothesize an effect of topical diclofenac epolamine plaster on limiting the increase of local concentrations of the pro-inflammatory prostaglandin PGE2 induced in the muscle of healthy human subjects following standardized physical exercise. No effect of diclofenac treatment on 8-iso-PGF2α concentrations was observed, mainly since isoprostane is produced by a free radical-catalyzed lipid peroxidation mechanism independent of cyclo-oxygenases.
Asunto(s)
Antiinflamatorios no Esteroideos , Diclofenaco/análogos & derivados , Dinoprost/análogos & derivados , Dinoprostona/análisis , Ejercicio Físico/fisiología , Músculo Cuádriceps/efectos de los fármacos , Administración Cutánea , Adulto , Antiinflamatorios no Esteroideos/administración & dosificación , Antiinflamatorios no Esteroideos/farmacocinética , Antiinflamatorios no Esteroideos/farmacología , Diclofenaco/administración & dosificación , Diclofenaco/farmacocinética , Diclofenaco/farmacología , Dinoprost/análisis , Relación Dosis-Respuesta a Droga , Voluntarios Sanos , Humanos , Masculino , Microdiálisis , Músculo Cuádriceps/metabolismo , Músculo Cuádriceps/fisiología , Parche Transdérmico , Adulto JovenRESUMEN
OBJECTIVES: Ertapenem pharmacokinetics were determined in the interstitium of healthy tissue and of infected tissue of patients suffering from diabetic foot infections, to evaluate if antibiotic concentrations at the target site are sufficient to achieve bacterial killing. PATIENTS AND METHODS: Nine patients with diabetic foot infections received 1 g of ertapenem per day intravenously. At steady-state, ertapenem concentrations were measured over 8 h in plasma and in the interstitium of healthy subcutaneous adipose tissue and of soft tissue adjacent to the foot infection using microdialysis. RESULTS: The maximum total concentration (Cmax) of ertapenem in plasma was 59.4 ± 12.9 mg/L. Free interstitial Cmax in the infected leg (4.5 ± 2.7 mg/L) was significantly higher (P=0.01) than in healthy subcutaneous tissue (2.4 ± 1.6 mg/L). For bacterial pathogens with an MIC of 1 mg/L, the free mean 'time above MIC' (T>MIC) in the interstitium of infected tissue was calculated to be 38%± 25% of the 24 h dosing interval. Accordingly, bacteriostatic (T>MIC >20%) and maximal bactericidal (T>MIC >40%) effects would be reached in 8/9 and 4/9 diabetic feet, respectively. CONCLUSIONS: Although total plasma concentrations of ertapenem were lower in diabetics than reported for healthy subjects, free interstitial tissue concentrations in diabetics were similar to those known from healthy volunteers. Penetration of ertapenem into the interstitium of inflamed tissue of diabetic feet was not impaired in spite of angiopathy. Daily doses of >1 g of ertapenem might be considered to optimize bactericidal effects in diabetic foot infections caused by moderately susceptible strains.
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Antibacterianos/administración & dosificación , Antibacterianos/farmacocinética , Infecciones Bacterianas/tratamiento farmacológico , Pie Diabético/complicaciones , Piel/química , beta-Lactamas/administración & dosificación , beta-Lactamas/farmacocinética , Administración Intravenosa , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Ertapenem , Femenino , Humanos , Masculino , Persona de Mediana Edad , Plasma/química , Piel/patología , Adulto JovenRESUMEN
The metabolic turnover, absolute oral bioavailability, clearance, and volume of distribution for ß-sitosterol were measured in healthy subjects. [(14)C]ß-Sitosterol was used as an isotopic tracer to distinguish pulse doses from dietary sources and was administered by both oral and intravenous routes. The administered doses of [(14)C]ß-sitosterol were in the region of 3 to 4 µg, sufficiently low as not to perturb the kinetics of ß-sitosterol derived from the diet. Because the plasma concentrations of [(14)C]ß-sitosterol arising from such low doses were anticipated to be very low, the ultrasensitive isotope ratio analytical method of accelerator mass spectrometry was used. The limit of quantification for [(14)C]ß-sitosterol was approximately 0.1 pg/ml, the oral absolute bioavailability was just 0.41%, clearance was 85 ml/h, volume of distribution was 46 L, and the turnover was 5.8 mg/day. Given the steady-state concentrations of ß-sitosterol (2.83 µg/ml), then the dietary load was calculated to be approximately 1400 mg/day.
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Hipolipemiantes/administración & dosificación , Hipolipemiantes/farmacocinética , Sitoesteroles/administración & dosificación , Sitoesteroles/farmacocinética , Administración Oral , Adolescente , Adulto , Área Bajo la Curva , Disponibilidad Biológica , Biotransformación , Radioisótopos de Carbono , Dieta , Semivida , Humanos , Hipolipemiantes/sangre , Inyecciones Intravenosas , Masculino , Espectrometría de Masas/métodos , Tasa de Depuración Metabólica , Persona de Mediana Edad , Modelos Biológicos , Sitoesteroles/sangre , Adulto JovenRESUMEN
AIMS: To compare the bioavailability of a new oromucosal formulation of flurbiprofen 8.75-mg lozenges, developed by Alfa Wassermann S.p.A. (test drug) to that of marketed flurbiprofen 8.75-mg lozenges (Benactiv Gola®, reference drug). METHODS: This was an open, randomised, two-period, crossover, pharmacokinetic (PK) study in which flurbiprofen plasma levels were compared in 12 healthy volunteers after the administration of single doses (8.75 mg × 2) of two different oromucosal lozenges to be sucked and slowly dissolved in the mouth. A wash-out period of at least 7 days separated the two study periods. Blood samples were collected prior to dosing and at predefined intervals for 24 h after dose. Flurbiprofen plasma concentrations were determined by liquid chromatography/tandem mass spectrometry. PK parameters maximum plasma concentration (C(max)), time to maximum plasma concentration (T(max)), area under the plasma concentration-time curve from time zero to 24 hours (AUC(0-t)), area under the plasma concentration-time curve from time zero to infinity (AUC(0-)∞) and half-life were calculated and compared by analysis of variance using treatment, period and sequence as sources of variation. Bioequivalence between the two formulations was based on 90% confidence intervals of the ratio of the geometric means of C(max) and AUC falling within the 0.80-1.25 range as defined in bioequivalence guidelines by regulators. Tolerability of the two formulations was assessed by adverse event monitoring, routine laboratory tests, physical examination, electrocardiographic tracing and vital sign measurements. RESULTS: All enrolled subjects completed the study. Bioequivalence without significant treatment effect was demonstrated between the test drug/reference drug ratios of mean C(max) and AUCs. Moreover, mean T(max) was superimposable. No safety parameter presented a clinically relevant variation after administration of either formulation that were therefore well tolerated. CONCLUSION: The new formulation of flurbiprofen 8.75-mg compressed lozenges developed by Alfa Wassermann S.p.A. is bioequivalent to the reference product flurbiprofen 8.75-mg lozenges (Benactiv Gola) in healthy volunteers.
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Analgésicos/farmacocinética , Antiinflamatorios no Esteroideos/farmacocinética , Flurbiprofeno/farmacocinética , Adolescente , Adulto , Analgésicos/administración & dosificación , Analgésicos/sangre , Antiinflamatorios no Esteroideos/administración & dosificación , Antiinflamatorios no Esteroideos/sangre , Área Bajo la Curva , Estudios Cruzados , Formas de Dosificación , Femenino , Flurbiprofeno/administración & dosificación , Flurbiprofeno/sangre , Humanos , Masculino , Persona de Mediana Edad , Adulto JovenRESUMEN
Acidification of urine is widely recommended for prevention and treatment of urinary tract infections. We set out to describe the effect of modification of pH on bacterial growth of relevant bacteria as well as on activity of modern fluoroquinolones in urine in vitro. Bacterial growth of Escherichia coli ATCC 25922 and Klebsiella oxytoca ATCC 700324 was determined in pooled human urine adjusted to pH levels between 5.0 and 8.0. Minimal inhibitory concentrations (MICs) and time-kill curves were performed for ciprofloxacin, levofloxacin and moxifloxacin in pH-adjusted urine and Mueller-Hinton Broth (MHB). Uptake of radioactive labeled [C(14)]-ciprofloxacin into bacterial cells was investigated at different pHs. While no difference in bacterial growth of E. coli and K. oxytoca was observed at pH values between 5.0 and 8.0, acidification of urine led to major impairment of antimicrobial activity of all tested fluoroquinolones, indicated by an up to 40-fold increase in MIC compared to MHB and nearly total neutralization of activity in time-kill experiments. The most probable mechanism behind this observation may have been reduced uptake of fluoroquinolones into bacterial cells, as indicated by bacterial uptake of [C(14)]-ciprofloxacin and a reversibility of the effect. The observed reduction in activity of modern fluoroquinolones confirms previous observations from older compounds.