Made available in DSpace on 2014-06-11T19:23:41Z (GMT). No. of bitstreams: 0 Previous issue date: 2012-02-16Bitstream added on 2014-06-13T19:50:42Z : No. of bitstreams: 1 rafael_la_me_botfmvz.pdf: 598677 bytes, checksum: 9244a6bf719ef84e48cb12aef3188a32 (MD5) / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) / Os processos sépticos são complicações frequentes nas estruturas sinoviais e demais tecidos da porção distal dos membros de equinos. A perfusão regional intravenosa é uma opção terapêutica, que objetiva aumentar significativamente a concentração de antimicrobiano na porção distal ao posicionamento do torniquete. No entanto, alguns pontos ainda não estão totalmente esclarecidos e algumas complicações, como trombose venosa, podem ocorrer. Objetivou-se com este estudo avaliar o potencial trombogênico da perfusão regional de gentamicina, na dose de 2,2 mg/kg na veia cefálica de equinos. Utilizou-se 15 equinos hígidos, divididos em três grupos de cinco animais. Grupo 1, somente torniquete (GT), grupo 2, torniquete e 40 ml de solução fisiológica (GSF), grupo 3, torniquete e gentamicina na dose de 2,2 mg/kg e solução fisiológica até completar um volume de 40 ml (GSG). Um membro torácico de cada animal foi escolhido aleatoriamente para o tratamento e torniquete aplicado no terço médio proximal do rádio. Ultrassonografia Doppler foi realizada no membro testado imediatamente antes, 30 minutos, 2, 3, 4, 6, 12, 24, 48, 72 e 96 horas após o tratamento na veia cefálica e artéria mediana. A artéria mediana também foi avaliada aproximadamente 15 minutos após posicionamento do torniquete. A termografia foi realizada em ambos os membros em todos os momentos. Os dados foram avaliados por análise de variância com medidas repetidas, teste de Tukey de comparações múltiplas de médias para comparar os grupos e ajustado para Dunnett para comparar os momentos em relação ao momento M0. Significância foi aceito p <0,05. Todos os grupos apresentaram escore trombótico zero, não houve diferença significativa entre os grupos quanto à temperatura do membro e diâmetro médio da veia. A perfusão regional intravenosa com... / Septic processes are common in synovial structures and tissues of the distal limbs in horses. Regional intravenous perfusion is a therapeutic option that aims to significantly increase the antibiotic concentration in the limb, distal to the tourniquet. Nevertheless, some critical points remains unclear, and complication such as thrombosis may occur along this procedure. The purpose of this work was to assess the thrombogenic potential of regional intravenous perfusion after administration of gentamicin in the cephalic vein. Fifteen healthy horses were assigned to three groups of 5 animals. Group 1, tourniquet group (TG), group 2, tourniquet and 40 mL of physiologic saline solution (SPG) and group 3, tourniquet and 2.2 mg/kg gentamicin completed to 40 mL by addition of physiologic saline solution (ASG). One forelimb of each animal was randomly chosen for treatment and tourniquet applied at the proximal end of the radius. Doppler ultrasonography was performed in the treated limb immediately before and 30 minutes, 2, 3, 4, 6, 12, 24, 48, 72 and 96 hours after treatment in the cephalic vein and artery median. The median artery was also evaluated approximately 15 minutes after placement of the tourniquet. Thermography was performed in both limbs at all the moments. Data were assessed by analysis of variance with repeated measures, Tukey's multiple mean comparison test to compare the groups and Dunnett's multiple mean comparison test to compare the moments regarding M0. Significance was accepted at p <0.05. Thrombotic score was zero for the three groups; no difference was found between groups regarding temperature and mean vein diameter of the treated limb. Regional intravenous perfusion using a single dose... (Complete abstract click electronic access below)

Orientador: Celso Antônio Rodrigues / Banca: Carlos Alberto Hussni / Banca: Luis Cláudio Lopes Correia da Silva / Resumo: Os processos sépticos são complicações frequentes nas estruturas sinoviais e demais tecidos da porção distal dos membros de equinos. A perfusão regional intravenosa é uma opção terapêutica, que objetiva aumentar significativamente a concentração de antimicrobiano na porção distal ao posicionamento do torniquete. No entanto, alguns pontos ainda não estão totalmente esclarecidos e algumas complicações, como trombose venosa, podem ocorrer. Objetivou-se com este estudo avaliar o potencial trombogênico da perfusão regional de gentamicina, na dose de 2,2 mg/kg na veia cefálica de equinos. Utilizou-se 15 equinos hígidos, divididos em três grupos de cinco animais. Grupo 1, somente torniquete (GT), grupo 2, torniquete e 40 ml de solução fisiológica (GSF), grupo 3, torniquete e gentamicina na dose de 2,2 mg/kg e solução fisiológica até completar um volume de 40 ml (GSG). Um membro torácico de cada animal foi escolhido aleatoriamente para o tratamento e torniquete aplicado no terço médio proximal do rádio. Ultrassonografia Doppler foi realizada no membro testado imediatamente antes, 30 minutos, 2, 3, 4, 6, 12, 24, 48, 72 e 96 horas após o tratamento na veia cefálica e artéria mediana. A artéria mediana também foi avaliada aproximadamente 15 minutos após posicionamento do torniquete. A termografia foi realizada em ambos os membros em todos os momentos. Os dados foram avaliados por análise de variância com medidas repetidas, teste de Tukey de comparações múltiplas de médias para comparar os grupos e ajustado para Dunnett para comparar os momentos em relação ao momento M0. Significância foi aceito p <0,05. Todos os grupos apresentaram escore trombótico zero, não houve diferença significativa entre os grupos quanto à temperatura do membro e diâmetro médio da veia. A perfusão regional intravenosa com... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: Septic processes are common in synovial structures and tissues of the distal limbs in horses. Regional intravenous perfusion is a therapeutic option that aims to significantly increase the antibiotic concentration in the limb, distal to the tourniquet. Nevertheless, some critical points remains unclear, and complication such as thrombosis may occur along this procedure. The purpose of this work was to assess the thrombogenic potential of regional intravenous perfusion after administration of gentamicin in the cephalic vein. Fifteen healthy horses were assigned to three groups of 5 animals. Group 1, tourniquet group (TG), group 2, tourniquet and 40 mL of physiologic saline solution (SPG) and group 3, tourniquet and 2.2 mg/kg gentamicin completed to 40 mL by addition of physiologic saline solution (ASG). One forelimb of each animal was randomly chosen for treatment and tourniquet applied at the proximal end of the radius. Doppler ultrasonography was performed in the treated limb immediately before and 30 minutes, 2, 3, 4, 6, 12, 24, 48, 72 and 96 hours after treatment in the cephalic vein and artery median. The median artery was also evaluated approximately 15 minutes after placement of the tourniquet. Thermography was performed in both limbs at all the moments. Data were assessed by analysis of variance with repeated measures, Tukey's multiple mean comparison test to compare the groups and Dunnett's multiple mean comparison test to compare the moments regarding M0. Significance was accepted at p <0.05. Thrombotic score was zero for the three groups; no difference was found between groups regarding temperature and mean vein diameter of the treated limb. Regional intravenous perfusion using a single dose... (Complete abstract click electronic access below) / Mestre

No / Aims To determine the bioavailability of gentamicin to the lung following inhalation from two jet nebulizers. Methods Serial urine samples were obtained from 10 volunteers after a 80 mg dose given orally, nebulized from a Pari LC + (PARI) and MicroNeb III (MN) devices, or after a 40 mg intravenous dose. In vitro aerodynamic characteristics of the nebulized doses were also determined. Results The mean (SD) absolute gentamicin lung bioavailalibility following delivery by PARI and MN devices was 1.4 (0.4) and 1.7 (0.5) %. The mass median aerodynamic diameter (MMAD) of the drug particles from the PARI and MN systems was 8.6 (0.6) and 6.7 (0.5) µm and the corresponding fine particle doses (FPD) were 10.2 (2.8) and 11.7 (1.5) mg. Conclusions The MMAD and FPD data reflect the poor lung deposition of gentamicin identified by urinary excretion.

Intracellular pathogens like <i>Salmonella</i> have developed various mechanisms to evade host defenses, and they can establish infections. Treatment and eradication are difficult due to our inability in achieving the optimum concentrations of cell-impermeable aminoglycosides like gentamicin within these cells. In this dissertation, we hypothesize that developing a novel core-shell methodology for incorporating high amounts of gentamicin into the cores with either hydrophilic or amphiphilic shell will be more effective than the free gentamicin in clearing intracellular <i>Salmonella</i> infection. Hydrophilic core-shell nanostructures (N1) were made with block co-polymers of poly (ethylene oxide-<i>b</i>-sodium acrylate) blended with sodium polyacrylate (PAA^-+Na) and complexed with the polycationic antibiotic gentamicin. N1 showed 20-25 fold higher gentamicin loading than the currently existing materials and reduced numbers of viable <i>Salmonella</i> in the liver and spleen compared to free gentamicin. To further improve the rate and route of uptake, the shell of the nanostructures were made amphiphilic by incorporating pluronics F68 (PPO)₆₈ in the block copolymer. We showed that core-shell nanostructures encapsulating gentamicin having (PPO)₆₈ in the shell (N2) enhances the rate and modulates the route of uptake into macrophages, thus promoting significant reduction in the intracellular <i>Salmonella in-vitro</i> and <i>in-vivo</i>. The main drawback of N2 was its poor stability at physiological pH of 7.4, 0.1 M NaCl. Therefore, core-shell nanostructures encapsulating gentamicin containing pluronic P85 (PPO)₈₅ in the shell (N3) with improved colloidal and ionic stability were designed. N3 achieved significant intracellular reduction of vacuolar <i>Salmonella</i> (0.53 log₁₀) and cytoplasm resident <i>Listeria</i> (3.11 log₁₀) compared to free gentamicin in-vitro. However, greater reduction of <i>Listeria</i> suggested that sub-cellular localization of bacterium influences targeting by N3. Even though oral administration of N3 was not effective compared to free gentamicin, parenteral (I.P.) administration significantly reduced the intracellular <i>Salmonella</i> from liver and spleen compared to free gentamicin and appeared to have no abnormal <i>in-vivo</i> toxicity. In summary, core-shell nanostructures encapsulating gentamicin (N) with improved encapsulation efficiency and different shell chemistry (N1, N2 and N3) were developed with enhanced efficacy against intracellular Salmonella. The novel gentamicin delivery approach developed in this study may be applicable for therapy of many intracellular infections. / Ph. D.

Ten polymethylmethacrylate (PMMA) beads containing metronidazole (3 concentrations); gentamicin sulfate; or metronidazole and gentamicin sulfate were immersed in 5 ml of phosphate buffered saline in triplicate. Eluent was replaced at specified time intervals for 1 day (1, 3, 6, 12 and 24 hours), daily, or weekly for 21 days. Antibiotic concentrations were measured by high performance liquid chromatography. Changes in antibiotic bioactivity attributable to polymerization or co-polymerization of the antibiotics with PMMA, ethylene oxide sterilization, and storage of antibiotic-impregnated PMMA (AIPMMA) beads containing metronidazole were evaluated. Antibiotic elution patterns were similar for all groups. Day-1 elution for groups containing either metronidazole (3 concentrations) or gentamicin represented a mean 63% to 66% and 79% respectively of the 21-day total elution. Approximately 50% of the day-1 elution occurred during the first hour. The elution of metronidazole was dose-dependent. There was no significant difference in the total amount of antibiotic eluted from groups that had the saline changed daily versus weekly. The elution of metronidazole (day 3-21) and gentamicin (all days) was significantly greater when metronidazole and gentamicin were combined (p<0.05). Polymerization of PMMA was delayed in groups containing metronidazole. Neither polymerization nor co-polymerization of metronidazole and gentamicin with PMMA, gas-sterilization, or 2-month storage of beads containing metronidazole significantly affected antimicrobial bioactivity. Metronidazole elutes from PMMA. The frequency at which the saline was changed did not affect the rate of antibiotic elution. Co-polymerization of metronidazole and gentamicin sulfate in PMMA resulted in increased rates of elution. Intra-operative preparation of metronidazole-impregnated PMMA beads is not practical. However, prefabrication of metronidazole or metronidazole-gentamicin beads, gas-sterilization and storage for up to 2 months should not affect the efficacy of either antibiotic. The local delivery of biologically active metronidazole and gentamicin by elution from PMMA is feasible. / Master of Science

Gentamicin is an aminoglycoside antibiotic that possesses bactericidal activity against many gram-positive and gram-negative organisms. Clinically, it is used most often to treat life-threatening infections due to Pseudomonas, Proteus, and the Klebsiella-Enterobacter group. A relationship between gentamicin serum concentrations and clinical response has been demonstrated. Toxicities, notably ototoxicity and nephrotoxicity, are also associated with serum concentrations. Gentamicin is given intermittently either intramuscularly or intravenously resulting in peak and trough concentrations. The therapeutic range is defined as peak concentrations between 4-15mg/L (depending in part on the site of infection and the susceptibility of the infecting organism), and trough concentrations less than 2mg/L (to minimize toxicity). Gentamicin distributes into a space similar to the extracellular fluid volume (ECFV). Pathophysiologic changes which alter the extracellular fluid compartment also alter gentamicin volume of distribution (Vd). One intrinsic factor known to alter gentamicin Vd is obesity. Leanness is also thought to alter gentamicin Vd but its effect has not been quantitated. The objectives of this study were to: 1) accurately describe a Vd in "normal" patients, that is, those with no factors known to alter gentamicin volume of distribution; 2) determine if there is a continuous linear relationship between gentamicin volume of distribution (L/kg) and percent body fat; 3) determine if that relationship is associated with changes in ECFV; and 4) develop a formula for predicting Vd in a similar patient population. Twenty patients with no extrinsic factors known to alter gentamicin Vd participated in the study. Five blood samples were drawn around one steady state dose of gentamicin. A one-compartment model was used to calculate Vd. Tritiated water and anthropometric measurements were conducted simultaneously to provide estimates of body composition. Together these values were used to examine the relationship between gentamicin Vd and body composition. We have described a Vd for gentamicin that is larger but no less variable than is currently used to determine initial dosage regimens. This volume may be larger either due to the selection of patients or method of serum gentamicin analysis. This larger volume should be used to calculate empiric dosage regimens for similarly selected patients to decrease the risk of treatment failure. We were not able to describe a linear relationship between percent body fat and gentamicin volume of distribution. We have postulated several reasons as to why this relationship could not be detected; 1) the sample size may not have been large enough, 2) the relationship is not important in patients who are not at extremes of weight, or 3) the variations caused by changes in body composition were not as significant as other factors that may cause fluid alterations in hospitalized patients. There was a strong correlation between gentamicin Vd and total body water noted. Having eliminated all patients in whom the relationship between total body water and ECFV could not be assumed to be normal and constant, we have indirectly demonstrated a strong relationship between ECFV and gentamicin Vd. This relationship still leaves variability in gentamicin's distribution characteristics to be explained. The predictive formula is based on measurements of height, weight, and a larger Vd [L/kg(ideal body weight)] than has previously been used. The predictive formula recommended for clinical use in adults is Vd=0.30L/kg (Dosing Weight). Dosing weight equals ideal body weight (IBW) when actual body weight (ABW) is ≤ IBW, or 0.4(ABW-IBW)+IBW, when ABW is > IBW. The consequences of estimating a larger Vd are that patients empirically would receive larger doses than are currently being administered, thus more patients should obtain therapeutic serum concentrations within the first 24 hours of therapy. This information will be useful in our attempts to optimize gentamicin therapy. / Pharmaceutical Sciences, Faculty of / Graduate

Antibióticos antimicrobianos são moléculas capazes de inibir o crescimento de microrganismos, na maioria, produtos naturais derivados de fungos ou bactérias que bloqueiam processos cruciais para a sobrevivência de microrganismos. A gentamicina é um aminoglicosídeo 4,6 bisubstituído que exerce papel importante no tratamento de infecções graves causadas por bactérias gram-negativas; apresenta uma complexa e pouco entendida rota de biossíntese. Dessa via, a desidrogenase GenD2 e a aminotransferase GenS2 atuam sobre a posição C3 da gentamicina A2 produzindo gentamicina X2, e a GenB2 atua na posição C6 epimerizando a molécula de gentamicina C2a. As enzimas foram purificadas por cromatografia de afinidade e por exclusão de tamanho, no tampão composto por 50 mM de Tris HCl, 100 mM de NaCl pH 7,7. Com a intenção de compreender a rota de biossíntese da gentamicina, o objetivo deste trabalho foi estudar estruturalmente as enzimas GenD2, GenS2 e GenB2 em complexo com seus cofatores e ligantes. Cristais da enzima GenD2 difrataram, porém não foi possível determinar sua estrutura, análises biofísicas através de calorimetria de titulação isotérmica e por gel filtração analítica, puderam confirmar seu cofator, o NAD+, e um estado oligomérico compatível à um tetrâmero em solução. A enzima GenB2 em complexo com o cofator PMP e gentamicina X2 difratou a uma resolução de 1,7 Å e foi resolvida por substituição molecular, na qual foi identificada uma molécula na unidade assimétrica pertencente ao grupo espacial C 2 2 21. Essa enzima é um homodímero, seu sítio de ligação está na interface entre os protômeros com contribuições de resíduos de ambas as moléculas. A região onde se encontra o anel pirimidínico do PMP é carregada positivamente, favorecendo a interação com o cofator. A cavidade onde se encontra posicionada a gentamicina X2, é bastante ampla e eletronegativa, por seu substrato ser um aminoglicosídeo. A lisina 227 é o resíduo que realiza a clássica base de Schiff, presente em enzimas PLP/PMP dependentes, entre o anel pirimidínico do PMP e a tirosina 124. Os avanços promissores sobre a GenD2 e a compreensão estrutural da GenB2 auxiliam no entendimento da via de biossíntese de gentamicina bem como contribuem para o crescente entendimento sobre o enovelamento de enzimas PLP dependentes. / Antimicrobial antibiotics are molecules capable of inhibiting the growth of microorganisms, most of them are natural products derived from fungi or bacteria that block some crucial processes to the survival of microorganisms. Gentamicin is a 4,6 disubstituted aminoglycoside that plays an important role in the treatment of severe infections caused by gram-negative bacteria. This aminoglycoside presents a complex and poorly understood biosynthesis route. From this route, GenD2 dehydrogenase and GenS2 aminotransferase have been identified to act at C3 position of gentamicin A2 producing gentamicin X2, and the enzyme GenB2 acts at the C6 position, epimerizing the gentamicin C2a molecule. These enzymes were purified by immobilized metal ion affinity and size exclusion chromatography in a buffer composed of 50 mM Tris HCl, 100 mM NaCl pH 7,7. In order to understand the route of gentamicin biosynthesis, this work aims to study the enzymes GenD2, GenS2 and GenB2 in complex with their cofactors and ligands. Some crystals of GenD2 diffracted, however it was not possible to determine its structure. Biophysical analysis by isothermal titration calorimetry and analytical gel filtration; confirmed NAD+ as its cofactor, and an oligomeric state compatible with a tetramer in solution. GenB2 crystals in complex with PMP cofactor and gentamicin X2 diffracted at a resolution of 1.7 Å and its structure was resolved by molecular replacement, which presented one molecule in the asymmetric unit belonging to the space group C 2 2 21. This enzyme is a homodimer, the binding site is located at the interface between protomers and residues from both molecules contribute toward the formation of the active site. The region where the PMP pyrimidine ring is located is positively charged, favoring the interaction with the cofactor. The active site cavity, where gentamicin X2 is positioned, is a large groove and predominantly electronegative, compatible with the substrate of the enzyme, which is an aminoglycoside. Lysine 227 is the key residue that performs the classical Schiff base, commonly present in PLP/PMP dependent enzymes, between the PMP pyrimidine ring and tyrosine 124. Promising advances on GenD2 and the structural understanding of GenB2 aids in the understanding of the gentamicin biosynthetic pathway as well as contribute towards the knowledge about the folding of PLP dependent enzymes.

Na medicina equina, procedimentos cirúrgicos ortopédicos, principalmente os que envolvem fixação de fratura, apresentam um grande índice de infecção e mortalidade. Diferentes métodos de liberação local de antibiótico têm sido utilizados com sucesso na profilaxia e tratamento das infecções musculoesqueléticas. O objetivo da presente investigação foi avaliar a capacidade da poliuretana de mamona como dispositivo de liberação local de antibiótico in vitro já que não existem relatos deste polímero para tal finalidade, além de analisar o efeito bactericida da gentamicina liberada pelo polímero. Foram confeccionados 40 corpos de prova de polímero de mamona, divididos igualmente em 4 grupos, sendo um grupo controle, este sem adição de sulfato de gentamicina e três grupos com diferentes concentrações de gentamicina (6, 12 e 24 mg/g de polímero), onde avaliou-se a liberação de gentamicina em solução PBS com pH 7,4 através da espectrofotometria colorimétrica com reação da ninhidrina em diferentes dias (01, 02, 07, 14, 21 e 28). A espectrofotometria colorimétrica com reação da ninhidrina não se mostrou o método de análise adequado para avaliar a liberação a partir deste polímero, porém a poliuretana de mamona mostrou-se efetiva como mecanismo de liberação de gentamicina quando avaliada in vitro em culturas de S. aureus. / In equine medicine, orthopedic procedures, especially those involving fracture fixation, presented a high rate of infection and mortality. Different methods of local release of antibiotics have been used successfully for prophylaxis and treatment of orthopaedic infections. The objective of this research was to evaluate the ability of castor oil polyurethane as a controlled release local antibiotic in vitro since there are no reports of this polymer for this purpose and the bactericidal effect of gentamicin released. Were prepared 40 samples of castor oil polymer, divided equally into four groups, one control group, without this addition of gentamicin sulfate and three groups with different concentrations of gentamicin (6, 12 and 24 mg / g of polymer) that was evaluated the release of gentamycin in PBS at pH 7.4 by spectrophotometry colorimetric reaction with ninhydrin in different days (01, 02, 07, 14, 21 and 28). The spectrophotometry colorimetric reaction with ninhydrin did not prove to be an appropriate method of analysis for assessing the release from this polymer, but the castor oil polyurethane proved to be an effective as a mechanism for release of gentamicin when evaluated in vitro in cultures of S. aureus

Tikslas: Įvertinti aminoglikozidų koncentracijos tyrimo svarbą racionaliai farmakoterapijai. Nustatyti ir įvertinti amikacino ir gentamicino koncentracijų tyrimų tendencijas Limoges universitetinėje ligonineje (CHU) ir Kauno medicinos universiteto klinikose (KMUK). Metodai: Duomenys buvo gauti iš CHU farmakologijos – toksikologijos ir statistikos skyrių bei KMUK klinikinės chemijos - hematologijos laboratorijos ir statistikos skyriaus. Apskaičiuota kiek koncentracijos tyrimo tenka vienam lovadieniui per 2007 metus, įvertintos gentamicino ir amikacino ištirtų koncentracijų duomenys bei paskirtos dozės. Duomenų statistinė analizė buvo atlikta naudojant MS Office programų paketo MS Excel skaičiuoklės ir duomenų apdorojimo programos. Rezultatai: Gentamicinui buvo atlikta 400 koncentracijos tyrimų (184 atvejų Cmax koncentracijai tirti, 216 – Cmin koncentracijai tirti) . Tirti 131 ligoniai (46 moterys ir 85 vyrai), kuriems gentamicino dozė individualiai adaptuota 221 kartą. Amikacinui buvo atlikta 169 koncentracijos tyrimai (82 atvejai Cmax koncentracijai tirti , 87 – Cmin koncentracijai tirti). Tirti 62 ligoniai (24 moterys ir 38 vyrai), kuriems amikacino dozė individualiai adaptuota 92 kartus. CHU tenka 6,85×10-4 (1:1460) gentamicino koncentracijos tyrimo vienam lovadieniui ir 2,89×10-4 (1:3456) amikacino koncentracijos tyrimo vienam lovadieniui.KMUK tenka 2,77×10-5 ( 1:36089) gentamicino koncentracijos tyrimo vienam lovadieniui. Taigi, CHU 24,72 kartais lenkia KMUK gentamicino... [toliau žr. visą tekstą] / Objectives: To evaluate the importance of researh on aminoglicozids for rational pharmacotherapy. To determine and evaluate the tendencies of studies of amikacin and gentamicin concentration in Limoges University Hospital (CHU) and Kaunas University of medicine Hospital (KMUM). Methods: The data has been received from the department of pharmacology and toxicology and the department of statistics of CHU and from the laboratory of chemistry and hematology and the department of statistics of KMUK. It has been calculated how much concentration study belongs to one bed-day in the year 2007, the data of the studied concentrations of gentamicin and amikacin have been evaluated and the doses have been administered. Statistical analysis of the data has been carried out by the use of MS Excel and data processing programs of MS Office. Results: 400 concentration studies have been carried out for gentamicin (184 cases for the study of Cmax concentration, 216 cases for the study of Cmin concentration). 131 patients (46 women and 85 men), who have been individually adapted the dose of gentamicin for 221 time, have been studied. 169 concentration studies have been carried out for amikacin (82 cases for the study of Cmax concentration, 87 cases for the study of Cmin concentration). 62 patients (24 women and 38 men), who have been individually adapted the dose of amikacin for 92 times. In CHU, there is 6.85×10-4 (1:1460) of gentamicin concentration study for one bed-day and 2.89×10-4 (1:345... [to full text]

Zugl.: München, Univ., Diss., 2008