Management of non-hepatic distant metastases in neuroendocrine neoplasms.

Neuroendocrine neoplasms represent an uncommon disease with an increasing incidence. Thanks to improvements in diagnostic and therapeutic methods, metastases previously considered uncommon, such as bone metastases, or even very rare, such as brain, orbital and cardiac metastases, are more frequently found in daily practice. Due to the great heterogeneity of these neoplasms, there is a lack of high-quality evidence on the management of patients with these types of metastases. The aim of this review is to provide the current state of the art, reviewing neuroendocrine neoplasm specific studies and useful information from other tumor types and to propose a treatment recommendation with algorithms to consider in daily clinical practice.

Long-term antibody response following SPUTNIK V primary vaccination in healthcare workers with and without history of SARS-CoV-2 infection: Prospective cohort study from a hospital in Argentina.

Background: In December 2020, Sputnik V was incorporated to the National COVID-19 Immunization Plan in Argentina. Studies had shown 98% of antibody response rate. To date, data on immunogenicity and antibody persistence in Argentina are scarce.The objective was to assess humoral immune response after two doses of Sputnik V in Health Care Workers (HCWs) at the Ricardo Gutierrez Children's Hospital (RGCH). Methods: A prospective, cohort study in HCWs immunized with two doses of Sputnik V between February and March 2021. The following variables were assessed: age, gender, risk factors for severe COVID-19 or mortality, immunosuppressive therapy and history of SARS-CoV-2. Blood samples were drawn on the day of the first dose, 28 days and 180 days after the second. Anti-Spike IgG was measured using an ELISA assay. Differences in immune response were evaluated according to study variables. Comparison analyses between groups with or without history of infection were performed, with T-test and ANOVA or Mann-Whitney tests. For each subject, we compared baseline values with 28 days and 180 days after the second vaccine.STATA version 14 and R Sofware were used for data analyses. Results: We included 528 individuals, mean age 41.5 years, 82.9% female, 14.4% (76/528) reported previous SARS-CoV-2 infection.All subjects developed antibodies post-vaccination. At day 28, concentrations were significantly higher in previously infected than naïve subjects (p < 0.001) with no differences according to age, gender and comorbidities.At day 180, 17% (95% CI 13.17-21.53) of naïve subjects were negative. Antibody concentrations decreased significantly in all subjects except in those who reported SARS-CoV-2 infection after vaccination (n = 31). This last group had significantly higher antibody concentrations. Conclusion: This study assessed immune response to a new COVID-19 vaccine in real life in a cohort of subjects. Antibody concentrations varied according to history of SARS-COV-2 infection and decreased over time.

Fipronil sulfone induced higher cytotoxicity than fipronil in SH-SY5Y cells: Protection by antioxidants.

Fipronil is a broad spectrum insecticide from the phenyl pyrazole family, which targets GABA receptor. Limited information is available about the metabolite fipronil sulfone cytotoxic actions. This study examined in vitro neurotoxicity of fipronil and fipronil sulfone and evaluated Trolox (vitamin E analog) (0.3, 1µM), N-acetyl-cysteine (0.5, 1mM), melatonin (0.1, 1µM) and Tempol (superoxide dismutase analog) (0.3, 0.5mM) protective role in SH-SY5Y cells. MTT and LDH assays were carried out to assess the cytotoxicity of fipronil and fipronil sulfone at 3-100µM concentrations. Fipronil sulfone was more toxic than fipronil. Tempol showed the best neuroprotectant profile against fipronil (50 and 150µM) and fipronil sulfone (3 and 10µM) reaching control levels. Fipronil (100µM) and fipronil sulfone (3µM) treatments induced a 4.7- and 5-fold increases in lipid peroxides measured as malondialdehyde (MDA) and a 2.2- and 2.0-fold increases in the levels of nitric oxide (NO). These results suggest that oxidative stress observed may be one of the major mechanisms of fipronil-induced neurotoxicity and it may be attributed in part to fipronil disposition and metabolism. Our results led us postulate that metabolite fipronil sulfone might be responsible for the fipronil-induced toxicity rather than fipronil itself.

Effects of exposure to pyrethroid cyfluthrin on serotonin and dopamine levels in brain regions of male rats.

The effects of cyfluthrin oral exposure (1, 5, 10 and 20mg/kg bw, 6 days) on brain region monoamine levels of male rats were examined. Cyfluthrin-treated rats (1, 5 and 10mg/kg bw, orally 6 days), had no visible injury, i.e., no clinical signs of dysfunction were observed. However, rats treated with cyfluthrin at the highest dose (20mg/kg bw, orally 6 days) showed skeletal muscle contraction in the hind limbs, slight movement incoordination without any signs of dyskinesia and tremor after 1-2h of treatment. These signs were reversible at 6h after dose. After last dose of cyfluthrin, dopamine (DA) and serotonin (5-HT) and its metabolites levels were determined in brain regions hypothalamus, midbrain, hippocampus, striatum and prefrontal cortex by HPLC. Cyfluthrin (1mg/kg bw, orally 6 days) did not affect the DA, 5-HT and metabolites levels in the brain regions studied. Cyfluthrin (5, 10 and 20mg/kg bw, orally 6 days) caused a statistically significant decrease in DA and its metabolites DOPAC and HVA levels and in 5-HT and its metabolite 5-HIAA levels in a brain region- and dose-related manner. Moreover, cyfluthrin (20mg/kg bw, orally 6 days) evoked a statistically significant increase in 5-HT turnover in striatum and midbrain, and in DA turnover in striatum and prefrontal cortex. These findings indicate that serotoninergic and dopaminergic neurotransmission is affected by exposure to cyfluthrin and may contribute to the overall spectrum of neurotoxicity caused by this pyrethroid.

Evidence for dose-additive effects of a type II pyrethroid mixture. In vitro assessment.

Despite the widespread use of pyrethroid insecticides that led to common exposure in the population, few studies have been conducted to quantitatively assess dose-additive effects of pyrethroids using a funcional measure involved in the common toxic mode of action. The aim of this study was to evaluate the potency and efficacy of 6 Type II pyretroids (α-cypermethrin, cyfluthrin, λ-cyhalothrin, deltamethrin, cyphenothrin and esfenvalerate) to evoke induction of both nitric oxide and lipid peroxides levels measured as malondialdehyde in three in vitro models (SH-SY5Y, HepG2 and Caco-2 human cells) as well as to test the hypothesis of dose additivity for mixtures of these same 6 pyrethroids. Concentration-responses for 6 pyrethroids were determined as well as the response to mixtures of all 6 pyrethroids. Additivity was tested assuming a dose-additive model. The human neuroblastoma SH-SY5Y cell line was the most sensitive in vitro model. The rank order of potency for cell SH-SY5Y viability MTT assay was deltamethrin>cyphenothrin>λ-cyhalothrin>cyfluthrin>esfenvalerate>α-cypermethrin. When 6 pyrethroids were present in the mixture at an equitoxic mixing ratio, the action on nitric oxide (NO) and lipid peroxides measured as malondialdehyde (MDA) production was consistent with a dose-additive model. The results of the present study are consistent with previous reports of additivity of pyrethroids in vivo e in vitro.

Differential induction of cytochrome P450 isoforms and peroxisomal proliferation by cyfluthrin in male Wistar rats.

Cyfluthrin effects on in vivo drug metabolizing enzymes were evaluated using the oxidative substrate antipyrine. Antipyrine pharmacokinetics in plasma and urinary excretion of its major metabolites with and without cyfluthrin oral treatment (20mg/kg/day for 6 days) were investigated in rats. Cyfluthrin increased the apparent intrinsic clearance and decreased the antipyrine half-life at ß phase. Cyfluthrin also increased the clearance of the antipyrine metabolites, norantipyrine, 4-hydroxyantipyrine and 3-hydroxymethylantipyrine and the formation rate constants for each of the three metabolites measured in urine. These results suggest that cyfluthrin affects hepatic cytochrome P450 (CYP) system. In order to confirm, a second experiment was carried out. We evaluated the effects of repeated exposure to cyfluthrin on hepatic and renal CYP2E, CYP1A and CYP4A subfamilies and peroxisomal proliferation in rats following oral administration (10 and 20mg/kg/day for 6 days). At the highest dose, cyfluthrin increased renal and hepatic O-deethylation of ethoxyresorufin and O-demethylation of methoxyresorufin, metabolism mediated by the CYP1A subfamily. Liver and kidney were susceptible to cyfluthrin-dependent induction of 12- and 11-hydroxylation of lauric acid, suggesting CYP4A subfamily induction. Also cyfluthrin increased the ß-oxidation of palmitoyl-coenzyme A and carnitine acetyltransferase activity, supporting cyfluthrin as a peroxisome proliferator. In conclusion, the demonstration that cyfluthrin induced hepatic CYP1A, CYP4A subfamilies and peroxisomal proliferation raises the possibility of cyfluthrin could produce changes in oxidative stress.

Effects of exposure to amitraz on noradrenaline, serotonin and dopamine levels in brain regions of 30 and 60 days old male rats.

The effects of amitraz oral exposure (20, 50 and 80mg/kg bw, 5 days) on brain region monoamine levels of male rats at 30 and 60 days of age were examined. The amitraz-treated rats at the oral doses of 20 and 50mg/kg bw had no visible injury, i.e., any clinical signs of dysfunction observed in any of the animals. However, rats treated with amitraz at the highest dose (80mg/kg bw, 5 days) showed a slight motor incoordination after 1-2h of treatment. These signs were reversible approximately at 6h after dose. After the last dose of amitraz, NE, DA and 5-HT and its metabolites levels were determined in the brain regions hypothalamus, midbrain, prefrontal cortex, striatum and hippocampus by HPLC. Amitraz caused changes in the NE, DA and 5-HT and their metabolite levels in a brain regional-, dose- and age-related manner. In the brain regions studied, amitraz induced a statistically significant increase in 5-HT, NE and DA content with age interaction, but the NE increases in prefrontal cortex and hippocampus was without age interaction. Moreover, in the brain regions studied, amitraz induced a statistically significant decrease in the metabolite 5-HIAA, MHPG, DOPAC and HVA levels displaying an age interaction, excepting the 5-HIAA decrease in midbrain and the DOPAC decrease in hypothalamus and striatum which were without age interaction. Furthermore, amitraz evoked a statistically significant decrease in 5-HT, NE and DA turnover in the brain regions studied. The present findings indicate that amitraz significantly altered CNS monoaminergic neurotransmitters in a brain regional-, dose- and age-related manner.

Effects of prenatal and postnatal exposure to amitraz on norepinephrine, serotonin and dopamine levels in brain regions of male and female rats.

The effects of maternal exposure to amitraz on brain region monoamine levels of male and female offspring rats at 60 days of age were observed. Maternal and offspring body weight, physical and general activity development were unaffected by the exposure of dams to amitraz (20mg/kgbw, orally on days 6-21 of pregnancy and 1-10 of lactation). Male and female offspring were sacrificed at 60 days of age and possible alterations in the content and metabolism of NE, DA and 5-HT were determined in brain regions by HPLC. The results showed that all these neurotransmitter systems were altered in a brain regional-related manner. In male and female offspring, amitraz induced a significant decrease in the prefrontal cortex 5-HT and its metabolite 5-HIAA and DA and its metabolites DOPAC and HVA levels with interaction of sex. Nevertheless, we verified that striatum DA and 5-HT and corresponding metabolite contents decreased in male and female offspring without statistical distinction of sex. In contrast, amitraz did not modify 5-HT content, but caused an increase in 5-HIAA content in the medulla oblongata and hippocampus in male and female offspring. Alterations in the hippocampus DA, DOPAC and HVA levels after amitraz exposure were also observed displaying a sex interaction. NE levels also showed a decrease after amitraz treatment in the prefrontal cortex and striatum without statistical sex interaction, but MHPG levels decreased in both regions with a sex interaction. Amitraz evoked increases in 5-HT turnover in the prefrontal cortex as well as in DA turnover in the striatum and hippocampus but decreases in NE turnover in the hypothalamus, prefrontal cortex and striatum. The present findings indicated that maternal exposure to amitraz altered noradrenergic, serotonergic and dopaminergic neurochemistry in their offspring in the prefrontal cortex, striatum and hippocampus, and those variations could be related to several alterations in the functions in which these brain regions are involved.

Toxicokinetics of glyphosate and its metabolite aminomethyl phosphonic acid in rats.

The toxicokinetics of glyphosate after single 100 mgkg(-1) intravenous (i.v.) and 400 mgkg(-1) oral doses were studied in rats. Serial blood samples were obtained after i.v. and oral administration. Plasma concentrations of glyphosate and its metabolite amiomethyl phosphonic acid (AMPA) were determined by HPLC method. After i.v. and oral administration, plasma concentration-time curves were best described by a two-compartment open model. For glyphosate, the elimination half-lives (T(1/2beta)) from plasma were 9.99 h after i.v. and 14.38 h after oral administration. The total plasma clearance was not influenced by dose concentration or route and reached a value of 0.995 l h(-1)kg(-1). After i.v. administration, the apparent volume of distribution in the second compartment (V(2)) and volume of distribution at steady state (V(ss)) were 2.39 and 2.99 l kg(-1), respectively, suggesting a considerable diffusion of the herbicide into tissues. After oral administration, glyphosate was partially and slowly absorbed with a T(max) of 5.16 h. The oral bioavailability of glyphosate was found to be 23.21%. Glyphosate was converted to AMPA. The metabolite AMPA represented 6.49% of the parent drug plasma concentrations. The maximum plasma concentrations of glyphosate and AMPA were 4.62 and 0.416 microg ml(-1), respectively. The maximum plasma concentration of AMPA was achieved at 2.42 h. For AMPA, the elimination half-life (T(1/2beta)) was 15.08 h after oral administration of glyphosate parent compound.

Historia clínica en soporte electrónico: experiencia de un servicio de Dermatología / Electronic medical history: Experience in a dermatology departament

La informatización consiste básicamente en una alternativa a la gestión clásica de la información, pasando del soporte en papel al electrónico. Este modelo aporta ventajas en la legibilidad, uniformidad, accesibilidad y explotación de los datos. Sin embargo, no es sencillo aplicar este proceso a la práctica clínica, pues requiere un adecuado soporte de equipos en red, el desarrollo continuo de las aplicaciones, una estrategia de implantación y la colaboración de todo el personal implicado. Revisamos nuestra experiencia en el desarrollo e implantación de una historia clínica (HC) en formato electrónico y su adaptación a un Servicio de Dermatología pionero en España. El modelo elegido en nuestro hospital desde su apertura en 1998 fue el de historia única centralizada electrónica de uso común (HCE) que se complementa con aplicaciones departamentales. La HCE se concibe como una base de datos relacional, centrada en el paciente y estructurada por procesos, que cumple los requisitos legales y permite prescindir del soporte físico (papel o placa) en la práctica totalidad de las situaciones. El sistema funciona en los servidores centrales bajo el mantenimiento del departamento de sistemas de información. Las potencialidades son ilimitadas, destacando: asistencia por guías de actuación clínica, conexión remota con Atención Primaria, gestión on-line de actividad, consumos y estándares de calidad. Buscando alcanzar estas potencialidades en 2003 se inició un cambio tecnológico hacia lo que después sería el sistema elegido en la Comunidad de Madrid para soportar el trabajo de los nuevos hospitales (AU)

Computerization, with a change from paper to electronic format, represents an alternative to traditional information management. This model offers advantages in legibility, uniformity, accessibility, and use of the data. However, it is not easy to apply this process to clinical practice as it requires a suitable network, continuous application development, an implementation strategy, and the cooperation of all staff involved. We have reviewed our experience in the development and introduction of electronic health records and their adaptation to a pioneer dermatology department in Spain. Since our hospital was opened 1998, the model used is that of a single, centralized electronic health record, with supplementary departmental attributes. The electronic health record is conceived as an interactive database designed around the patient, with a procedure-based structure, and that obviates the need for hardcopies (paper or films) in practically all situations; it must comply with legal requirements. The system is installed on central servers maintained by the information technology department. The potential is unlimited; particularly important possibilities include clinical guideline-directed care, remote connection for general practitioners, and online activity, stock, and quality management. With the aim of realizing this potential, a technological change was started in 2003, moving towards what was to become the chosen system in the Community of Madrid to cope with the workload arising from new hospitals (AU)

[Electronic medical history: experience in a dermatology department]. / Historia clínica en soporte electrónico: experiencia de un servicio de Dermatología.

Computerization, with a change from paper to electronic format, represents an alternative to traditional information management. This model offers advantages in legibility, uniformity, accessibility, and use of the data. However, it is not easy to apply this process to clinical practice as it requires a suitable network, continuous application development, an implementation strategy, and the cooperation of all staff involved. We have reviewed our experience in the development and introduction of electronic health records and their adaptation to a pioneer dermatology department in Spain. Since our hospital was opened 1998, the model used is that of a single, centralized electronic health record, with supplementary departmental attributes. The electronic health record is conceived as an interactive database designed around the patient, with a procedure-based structure, and that obviates the need for hardcopies (paper or films) in practically all situations; it must comply with legal requirements. The system is installed on central servers maintained by the information technology department. The potential is unlimited; particularly important possibilities include clinical guideline-directed care, remote connection for general practitioners, and online activity, stock, and quality management. With the aim of realizing this potential, a technological change was started in 2003, moving towards what was to become the chosen system in the Community of Madrid to cope with the workload arising from new hospitals.

An autopsy case of acute pulmonary toxicity related to irinotecan

No disponible

[Hereditary hemorragic telangiectasia: the state of art]. / Teleangectasia emorragica ereditaria: stato dell'arte.

Hereditary Hemorrhagic Telangiectasia (HHT) or Rendu-Osler-Weber syndrome, is a multisystemic vascular dysplasia. The disease is transmitted as a dominant autosomic character. The Hereditary Hemorrhagic Telangiectasia is differentiated in two subclasses: (1) HHT1, which is caused by mutation of ENG gene. This gene is localized on long arm of chromosome 9: (2) HHT2, which is caused by mutation of ALK-1 gene. This gene is located on long arm of chromosome 12. These two genes codify for two receptorial proteins: the endoglin and the activin-like protein 1; these proteins belong to receptorial superfamily of TGF-beta, which is involved in vascular remodelling and angiogenesis. Clinically, the consequences of these mutations are represented by the formation of cutaneous and/or mucous telangiectases and artero-venous fistulas. In both cases histological alteration is the same: extremely ectatic venules with numerous layers of myocytes around them. Arterioles communicate with venules directly without a capillary filter. Essentially, telangiectases manifest themselves with hemorrhages, while more common consequences of fistulas are secondary to formation of shunts with a possible thromboembolism; that is particularly serious in case of pulmonary artero-venous malformations. In 2000. Shovlin published 4 diagnostic criteria (criteria of Curaçao): (1) spontaneous and recurrent epistaxis; (2) multiple telangiectases; (3) visceral artero-venous malformations; (4) familiarity for HHT. Actually there is no possibility for a genetic therapy of HHT. Therefore, the therapeutic efforts are turned to control of symptoms and to the prevention of complications.

[Therapy of dyslipidemia in post-infarction: state of the art]. / Terapia delle dislipidemie nel post-infarto: stato dell'arte.

Between the risks factors involved in the atherogenesis LDL-cholesterol is determinant because highly associated to cardiovascular events. The primary target for the prevention of coronary diseases is a reduction of LDL-cholesterol because that reduces the cardiovascular mortality and the total mortality. The NCEP ATP III 2004 guide-lines propose as therapeutic target for the high-risk patients the reduction of plasma levels of LDL-cholesterol under 100 mg/dl and according to new trials under 70 mg/dl. The dyslipidaemia treatments are based on two approaches, i.e., the therapeutic lifestyle change and the pharmacological therapy. The available drugs are statins, fibrates, anion exchange resins, nicotinic acid. In the acute coronary syndrome patients is desirable to start immediately a therapy with statins since the hospital phase and direct the treatment to aggressive therapy. Unfortunately, the statin doses used in the most secondary prevention trials allow to get LDL-cholesterol under 100 mg/dl in the only half high-risk patients. The innovative therapeutic approach to hypercholesterolemia today is based on a double inhibition of cholesterol synthesis and absorption combining a statin with ezetimibe.

[Atypical presentation of syringocystoadenoma papilliferum]. / Siringocistoadenoma papilífero de presentación atípica.

Syringocystoadenoma papilliferum is benign adnexal tumor derived from the sweat glands that is located in the head and neck in 70-80% of patients, and commonly presents as a papule or a solitary nodule. We report a case of syringocystoadenoma papilliferum with an atypical presentation given its location in the thigh and the peculiar histologic features, unrepresentative of this entity.

Siringocistoadenoma papilífero de presentación atípica / Atypical presentation of syringocystoadenoma papilliferum

El siringocistoadenoma papilífero es un tumor anexial benigno derivado de las glándulas sudoríparas que en un 70-80 % de los pacientes se localiza en cabeza y cuello, generalmente en forma de pápula o nódulo solitario. Presentamos un caso de siringocistoadenoma papilífero inusual tanto por su localización, en un muslo, como por sus rasgos histológicos no estereotípicos de esta entidad

Syringocystoadenoma papilliferum is benign adnexal tumor derived from the sweat glands that is located in the head and neck in 70-80 % of patients, and commonly presents as a papule or a solitary nodule. We report a case of syringocystoadenoma papilliferum with an atypical presentation given its location in the thigh and the peculiar histologic features, unrepresentative of this entity

Psychological impact of sports activity in spinal cord injury patients.

OBJECTIVE: To investigate whether sports activity is associated with better psychological profiles in patients with spinal cord injury (SCI) and to evaluate the effect of demographic factors on psychological benefits. METHODS: The State-Trait Anxiety Inventory, Form X2 (STAI-X2), the Eysenck Personality Questionnaire for extraversion (EPQ-R (E)) and the questionnaire for depression (QD) were administered in a cross-sectional study of 137 males with spinal cord injury including 52 tetraplegics and 85 paraplegics. The subjects were divided into two groups according to sports activity participation (high frequency vs no sports participation). Moreover, multiple regression analysis was adopted to investigate the influence of demographic variables, such as age, educational level, occupational status and marital status, on psychological variables. RESULTS: Analysis of variance revealed significant differences among the groups for anxiety (STAI-X2), extraversion (EPQ-R (E)) and depression (QD). In particular, SCI patients who did not practice sports showed higher anxiety and depression scores and lower extraversion scores than sports participants. In addition, with respect to the paraplegics, the tetraplegic group showed the lowest depression scores. Following multiple regression analysis, only the sports activity factor remained as an independent factor of anxiety scores. CONCLUSION: These findings demonstrate that sports activity is associated with better psychological status in SCI patients, irrespective of tetraplegia and paraplegia, and that psychological benefits are not emphasized by demographic factors.

Effect of resistance training on risk of coronary artery disease in women with multiple sclerosis.

The effects of a lower-extremity progressive resistance-training program (PRT) on risk factors for coronary artery disease (CAD) were determined in patients with multiple sclerosis (MS). Twelve ambulatory women with MS (47.3+/-4.7 years; Expanded Disability Status Score (EDSS), 4.00+/-1.37) completed twice weekly lower-body PRT for 8 weeks. Knee extensor and ankle flexor strength improved significantly (p<0.05) after training, and self-reported fatigue decreased (p<0.05). Serum triglyceride concentrations decreased (p<0.05) but body-weight and fatness, blood pressure, and serum glucose, total cholesterol and high-density lipoprotein cholesterol were unchanged. However, the number of CAD risk factors that reached the clinical threshold for each subject declined after PRT, suggesting that resistance training can promote CAD risk reduction in ambulatory female MS subjects.

Resistance training improves strength and functional capacity in persons with multiple sclerosis.

The purpose of this study was to evaluate the effect of an eight-week progressive resistance training programme on lower extremity strength, ambulatory function, fatigue and self-reported disability in multiple sclerosis (MS) patients (mean disability score 3.7 +/- 0.8). Eight MS subjects volunteered for twice weekly training sessions. During the first two weeks, subjects completed one set of 8-10 reps at 50% of maximal voluntary contraction (MVC) of knee flexion, knee extension and plantarflexion exercises. In subsequent sessions, the subjects completed one set of 10-15 repetitions at 70% of MVC. The resistance was increased by 2-5% when subjects completed 15 repetitions in consecutive sessions. Isometric strength of the quadriceps, hamstring, plantarflexor and dorsiflexor muscle groups was assessed before and after the training programme using an isokinetic dynamometer. Magnetic resonance images of the thigh were acquired before and after the exercise programme as were walking speed (25-ft), number of steps in 3 min, and self-reported fatigue and disability. Knee extension (7.4%), plantarflexion (52%) and stepping performance (8.7%) increased significantly (P < 0.05). Self-reported fatigue decreased (P < 0.05) and disability tended to decrease (P = 0.07) following the training programme. MS patients are capable of making positive adaptations to resistance training that are associated with improved ambulation and decreased fatigue.

Pharmacokinetics of amoxycillin and the rate of depletion of its residues in pigs.

Six pigs were used in a two-period crossover study to investigate the pharmacokinetics of amoxycillin after single intravenous and oral doses of 20 mg/kg bodyweight. Twelve pigs were used to study the residues of the drug in muscle, kidney, liver and fat after they had received daily oral doses of 20 mg/kg amoxycillin for five days. The mean (sd) elimination half life (t1/2beta) and mean residence time of amoxycillin in plasma were 3.38 (0.30) and 3.54 (0.43) hours, respectively, after intravenous administration and 4.13 (0.50) and 4.47 (0.30) hours, respectively, after oral administration. After oral administration, the maximum plasma concentration (Cmax) was 7.37 (0.42) microg/ml and it was reached after 0.97 (0.29) hours. Six days after the last oral dose, the mean concentration of amoxycillin in the pigs' kidneys was 21.38 ng/g and in the liver it was 12.32 ng/g, but no amoxycillin could be detected in fat or muscle; the concentrations of amoxycillin in edible tissues were less than the European Union maximal residue limit of 50 microg/kg.