Siauro terapinio indekso vaistų vartojimas ir farmakokinetikos tyrimų interpretavimas reikalauja specialių farmakokinetikos žinių. Mokslinės literatūros šaltiniuose teigiama, jog gydymo procese dalyvaujant klinikiniams vaistininkams vaistų vartojimas yra optimizuojamas. Lietuvoje panašios vaistininkų veiklos nėra, todėl tyrimo tikslas buvo įvertinti siauro terapinio indekso vaistų vartojimo racionalumą ir nustatyti klinikinės farmacijos paslaugos poreikį stacionarinio gydymo įstaigoje. Darbo uždaviniai: nustatyti ir įvertinti farmakoterapinių problemų, siejamų su siauro terapinio indekso vaistų (vankomicino, ciklosporino, digoksino, gentamicino) vartojimu, paplitimą tretinio lygio ligoninėje; kiekybiškai ir kokybiškai įvertinti nustatytų farmakoterapinių problemų rizikos veiksnius; įvertinti vankomicino farmakokinetikos stebėsenos praktiką ligoninės skyriuose; įvertinti farmacininko konsultacijos įtaką vankomicino farmakokinetikos stebėsenai. Tyrimui pasirinktų siauro terapinio indekso vaistų farmakokinetikos tyrimų analizė atskleidė klinikinės farmacijos paslaugos poreikį optimizuojant tokių vaistų vartojimą Lietuvos ligoninėse. Nustatytų farmakoterapinių problemų rizikos veiksnių analizė identifikavo praktikoje dar visuotinai nepripažintą padidintą inkstų klirensą ir jo reikšmingą įtaką vaistų veiksmingumui. / The prescription of narrow therapeutic index drugs (NTID) and interpretation of pharmacokinetic measurements require special pharmacokinetic knowledge. Scientific publications report that active participation of clinical pharmacists in the treatment process results in optimization of the drugs use. In Lithuania, there are no similar services provided by pharmacists up till now. Aim of the study: to evaluate the rationality of the use of NTIDs and to determine the demand for clinical pharmacy services in hospitals. Objectives of the study: to identify and evaluate the prevalence of drug-related problems associated with the use of NTIDs (vancomycin, cyclosporine, digoxin, and gentamicin) in the tertiary-level hospital; to perform quantitative and qualitative analysis of risk factors for the identified drug-related problems; to evaluate the practice of pharmacokinetic vancomycin monitoring in hospital departments; to evaluate the influence of pharmacist intervention on pharma¬cokinetic vancomycin monitoring. The analysis of pharmacokinetic measurements of NTIDs selected for this study revealed the demand for clinical pharmacy services while optimizing NTIDs use in the Lithuanian hospitals. The analysis of risk factors associated with the identified drug-related problems identified augmented renal clearance, which is not widely acknowledged in practice, and its significant impact on the effectiveness of drugs.

?rea de concentra??o: Qu?mica anal?tica. / Submitted by Jos? Henrique Henrique (jose.neves@ufvjm.edu.br) on 2016-12-21T13:02:41Z No. of bitstreams: 2 license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) glauber_antonio_reis_andrade.pdf: 2400963 bytes, checksum: 99ec593844d6ba3a1107158d86656739 (MD5) / Approved for entry into archive by Rodrigo Martins Cruz (rodrigo.cruz@ufvjm.edu.br) on 2017-01-21T11:09:00Z (GMT) No. of bitstreams: 2 license_rdf: 9 bytes, checksum: 42dd12a06de379d3ffa39b67dc9c7aff (MD5) glauber_antonio_reis_andrade.pdf: 2400963 bytes, checksum: 99ec593844d6ba3a1107158d86656739 (MD5) / Made available in DSpace on 2017-01-21T11:09:00Z (GMT). No. of bitstreams: 2 license_rdf: 9 bytes, checksum: 42dd12a06de379d3ffa39b67dc9c7aff (MD5) glauber_antonio_reis_andrade.pdf: 2400963 bytes, checksum: 99ec593844d6ba3a1107158d86656739 (MD5) Previous issue date: 2016 / A Teofilina (TF), Clindamicina (CM), Varfarina (VF) e Verapamil (VP) s?o f?rmacos de baixo ?ndice terap?utico que necessitam de um controle de qualidade rigoroso na elabora??o de suas formula??es. O desenvolvimento de m?todos mais simples e r?pidos para doseamento desses medicamentos ? de grande interesse no setor farmac?utico. Neste sentido, o presente trabalho apresenta uma nova metodologia para determina??o desses f?rmacos por amperometria de m?ltiplos pulsos (MPA) acoplada ao sistema de an?lise por inje??o em batelada (BIA), utilizando o eletrodo de Diamante dopado com Boro (DDB). A an?lise em BIA foi realizada em uma c?lula eletroqu?mica do tipo Wall Jet, onde as inje??es foram realizadas por meio de uma micropipeta autom?tica ou, manualmente, por uma seringa descart?vel para TF, CM e VF, mostrando a possibilidade de diminuir custo do sistema de an?lise. O comportamento eletroqu?mico da TF, CM, VF e VP foi investigado por voltametria c?clica e os eletr?litos suportes escolhidos foram o ?cido sulf?rico 0,1 mol L-1, tamp?o fosfato 0,1 mol L-1 (pH 7,0), tamp?o fosfato 0,1 mol L-1 (pH 7,0) com 10% de ?lcool et?lico e ?cido sulf?rico 0,2 mol L-1, respectivamente. Nesses eletr?litos tr?s f?rmacos apresentaram um ?nico processo de oxida??o: a TF em +1,33V, a CM em +1,18 V e a VF em +0,90 V. J? o VP apresentou tr?s processos de oxida??o entre +1,2V e +1,5V, al?m de um processo de redu??o em +0,2V depende das oxida??es. A detec??o MPA-BIA foi baseada na aplica??o de um pulso de potencial de detec??o e outro de limpeza do DDB para tr?s f?rmacos. Neste caso, os pulsos de potencial para detec??o da TF, CM e VF foram todos aplicados por 100ms em +1,5V, +1,6V e +1,2V, respectivamente. Para determina??o do VP foram utilizados tr?s pulsos de potencial, um para oxida??o do VP (gerador) em +1,6V/50ms, um para redu??o do produto gerado (coletor) e quantifica??o do VP em -0,1V/30ms, e um terceiro em +1,1V/100ms para limpeza da superf?cie do DDB. A velocidade de inje??o da MA foi otimizada em 100?L s-1, exceto para VP que foi de 47?Ls-1, e com a SD a velocidade de inje??o foi de aproximadamente 107 ?Ls-1 pra a TF, CM e VF, proporcionando uma frequ?ncia anal?tica te?rica de pelo menos 53 determina??es por hora desses f?rmacos. Um baixo desvio padr?o relativo (10 medidas) foi obtido para todos os f?rmacos, n?o ultrapassando 3,0% tanto pela inje??o autom?tica quanto pela manual. As curvas anal?ticas foram estabelecidas e uma boa faixa linear foi obtida para todos os f?rmacos com pelo menos duas ordens de concentra??o. Os coeficientes de correla??o linear para todas as regress?es foram maiores que 0,992 em todos os estudos. Os estudos de adi??o e recupera??o mostraram valores pr?ximos a 100 % para todas as amostras farmac?uticas analisadas. O m?todo proposto usando a inje??o autom?tica e manual foi devidamente validado pelo m?todo oficial para cada um dos f?rmacos avaliados. Portanto, a detec??o MPA-BIA usando o eletrodo de DDB mostrou ser uma alternativa mais simples e r?pida para determina??o da TF, CM, VF e VP em formula??es farmac?uticas, possibilitando ainda uma diminui??o do custo do sistema BIA pela substitui??o da micropipeta autom?tica por uma seringa descart?vel. / Disserta??o (Mestrado) ? Programa de P?s-Gradua??o em Qu?mica, Universidade Federal dos Vales do Jequitinhonha e Mucuri, 2016. / Theophylline (TF), Clindamycin (CM), Warfarin (VF) and Verapamil (VP) are drugs of narrow therapeutic index that require a strict quality control in the preparation of their formulations. Thus, the development of simple and rapid methods for determination of these drugs is very important in the pharmaceutical industry. In this sense, this paper presents a new methodology for determination of these drugs by multiple-pulse amperometry (MPA) coupled to batch injection analysis (BIA), using the boron-doped diamond (BDD) electrode. The analysis in BIA system was performed in an electrochemical cell (Wall Jet), where the injections were performed by automatic micropipette or manually by an disposable syringe for TF, CM and VF, showing a possibility to reduction of the analysis cost. The electrochemical behavior of the analytes was investigated by cyclic voltammetry and the support electrolytes were chosen for TF, CM, VF and VP in medium of sulfuric acid 0.1 mol L-1, phosphate buffer 0.1 mol L-1 (pH 7.0), phosphate buffer 0.1 mol L-1 (pH 7.0) with 10% ethyl alcohol and sulfuric acid 0.2 mol L-1, respectively. In these conditions, three drugs exhibited a single oxidation process: TF in +1.33V, the CM in +1.18V and the VF in +0.90V (vs Ag/AgCl). Already the VP presented three oxidation processes between +1.2V and +1.5V, besides a reduction process in +0.20 V that depends on the oxidation. The MPA-BIA detection for three drugs (TF, CM, VF) was based on the application of two potential pulses, one for detection and other for cleaning BDD electrode. In this case, the potential pulses to detection the TF, CM and VF were all applied for 100ms at +1.5V, +1.2V and +1.6 V, respectively. In determination of the VP, were used three potential pulses, one for oxidation of VP (generator potential pulse) in +1.6V/50ms, one for reducing the generated product (collector potential pulse) and performed quantification of VP in -0.1V/30ms, and a third potential pulse at +1.1V/100ms for cleaning BDD electrode. The injection speed using automatic micropipette was 100?L s-1, except for VP that was 47?Ls-1, and injection speed by insulin syringe was approximately 107?Ls-1, which provide theoretical analytical frequency of at least 53 determinations per hour of these drugs. A low standard relative deviation (10 measures) was obtained for all drugs, not extending beyond 3.0% by both injections systems. The analytical curves were established and a good linear range was obtained for all drugs with at least two orders of concentration. The linear correlation coefficients for all regressions were higher than 0.992. The addition and recovery studies show values close to 100% for all drug samples analyzed. The proposed method using automatic and manual injection was validated by official method for each analyte. Therefore, this paper presented a fast and simple method for the determination of TF, CM, VF and VP in pharmaceutical formulations using BIA-MPA detection with BBD electrode. Moreover, this work demonstrated an inexpensive method for application in routine analysis of narrow therapeutic index drugs, mainly using a manual injection in BIA system by an disposable syringe.