Introdução e Objetivos: A circulação extracorpórea (CEC) pode alterar a cinética de fármacos, inclusive dos antibióticos. O objetivo deste estudo foi avaliar influência da CEC sobre a farmacocinética da cefuroxima e verificar se o esquema posológico proposto: 1, 5g em bolus, seguido por três bolus de 750 mg 6/6 horas por 24 horas, mantém concentrações plasmáticas adequadas em pacientes submetidos à revascularização do miocárdio (RM). Método: Foi realizado estudo prospectivo observacional com grupo controle comparando 10 pacientes submetidos à RM com CEC e 9 pacientes submetidos à RM sem CEC (Registro Clincal trials: NCT0122882). Amostras sanguineas foram coletadas sequencialmente após cada dose de antibiótico e analisadas por meio do método de cromatografia líquida de alta pressão (HPLC). Análise de variância (ANOVA) foi utilizada para a comparação das concentrações plasmáticas e Log-rank para comparar as curvas que avaliaram o tempo, após a administração da cefuroxima, para que fossem atingidas concentrações abaixo de 16 g/mL (quatro vezes a MIC- mínima inhibitory concentration); considerando p< 0,05. Resultados: A CEC com tempo médio de 59,7 min 21,1 minutos não alterou a farmacocinética ou as concentrações plasmáticas da cefuroxima. O clearance médio dp (mL/ Kg/ min) e a mediana da concentração mínima (mg/ dL) do grupo RM com CEC versus RM sem CEC foram 1,7 0,7 versus 1,6 0,6 (p= 0,67) e 6,1 versus 5,7 (p= 0,77), respectivamente. Ambos os grupos apresentaram diminuição nas concentrações plasmáticas influenciadas somente pelo tempo, após cada bolus de cefuroxima (p< 0,001). Concentrações acima de quatro vezes a MIC foram mantidas por três horas, por todos os pacientes, porém, após seis horas do primeiro bolus a probabilidade de manutenção das mesmas concentrações foi de 0,2 para o grupo RM com CEC e de 0,44 para o grupo RM sem CEC, p= 0,867. Após os demais bolus concentrações abaixo de 16 g/mL foram atingidas antes de três horas. Conclusão: A CEC não influenciou as concentrações plasmáticas ou a farmacocinética da cefuroxima. Os resultados da farmacocinética devem ser considerados para a escolha de um melhor esquema posológico / Background and Objectives: Cardiopulmonary bypass (CPB) can alter the kinetic of drugs, including antibiotics. The aim of this study was evaluation of the CPB influence on the plasma concentrations and pharmacokinetics of cefuroxime and assess whether the dosing regimen 1.5 g dose, followed by 750 mg 6/6h for 24h is adequate for antibiotic prophylaxis. Methods: A prospective controlled observational study compared 10 patients undergoing surgery with CPB and 9 submitted to off-pump surgery, (Clinical trials identifier: NCT0122882). After each cefuroxime dose, blood samples were sequentially collected and analyzed using high-efficiency chromatography (HPLC). Plasma concentrations were compared using variance analysis and log-rank test was employed to evaluate the differences between curves that quantified the fraction of patients with a remaining plasma concentration above 16 mg/L within 6 h after each bolus; considering P < 0.05 significant. Results: After each cefuroxime bolus, both groups presented a significant decrease in plasma concentration over time (p< 0.001). Mean CPB time of 59.7 ± 21.1 min did not change cefuroxime pharmacokinetics or plasma concentrations. The mean clearance ± SD (mL/kg/min) and median of minimum concentration (mg/dL) of the CPB group versus the off-pump group were 1.7 ± 0.7 versus 1.6 ± 0.6 (p= 0.67) and 6.1 versus 5.7 (p= 0.77), respectively. Up to 3 h, but not after 6 h, following the first bolus, all patients had plasma concentrations above 16 mg/L (CPB group= 0.2 and off-pump group= 0.44, p=0.867). After another bolus, concentrations below 16 mg/dL were reached before 3 h. Conclusions: CPB does not influence cefuroxime plasma concentration, but pharmacokinetic data should be considered when choosing intervals between doses

Este trabalho descreve o comportamento eletroquÃmico dos antibiÃticos cefuroxima (CFX) e cefalexina (CFA) por voltametria cÃclica (VC) e o desenvolvimento de metodologia eletroanalÃtica por voltametria de onda quadrada (VOQ) para a determinaÃÃo de CFX e de CFA sobre eletrodo de gota pendente de mercÃrio (HMDE, do inglÃs Hanging Mercury Drop Electrode). CFX apresentou dois processos catÃdicos irreversÃveis em -0,35 V (pico 1) e em -1,03 V (pico 2), com a participaÃÃo de dois elÃtrons e dois prÃtons tanto para o pico 1 como para o pico 2. Sugere-se que a reaÃÃo de reduÃÃo da molÃcula de CFX ocorre no grupo â C = N â para o pico 1 e no grupo â CH2 â R para o pico 2. Os parÃmetros experimentais e voltamÃtricos foram otimizados, com as respostas sendo obtidas em tampÃo BR pH 2,0,f = 90 s-1, a = 30 mV e &#916;Es = 2 mV. Os limites de detecÃÃo (LD) e de quantificaÃÃo (LQ) foram calculados utilizando-se o pico 1, com LD = 4,92x10-9 mol L-1 e LQ = 1,64x10-8 mol L-1 e recuperaÃÃo 109,15% com desvio padrÃo relativo (RSD, do inglÃs Relative Standart Deviation) de 2,39% (n = 3) em eletrÃlito de suporte. A metodologia desenvolvida foi aplicada em amostras de medicamentos, leite bovino e Ãguas naturais, com recuperaÃÃes variando de 96,40 a 129,4%. Para CFA constatou-se a presenÃa de processos catÃdicos em -0,97 V (pico 1) e em -1,2 V (pico 2). Nesse caso, tem-se que a reduÃÃo ocorre na dupla ligaÃÃo do grupo etilÃnico envolvendo a transferÃncia de dois elÃtrons e dois prÃtons. Os parÃmetros experimentais e voltamÃtricos foram avaliados com as respostas otimizadas sendo obtidas em tampÃo BR pH 2,0, f = 100 s-1, a = 30 mV e &#916;Es = 4 mV. Considerando-se o pico em -1,2 V, curvas analÃticas foram construÃdas, a partir delas os limites de detecÃÃo e de quantificaÃÃo foram calculados, LD = 1,27x10-8 mol L-1 e LQ = 4,23x10-8 mol L-1 com recuperaÃÃo de 89,19% com RSD = 1,51% (n = 3) em eletrÃlito de suporte. A metodologia foi aplicada na quantificaÃÃo de amostras de medicamentos, leite bovino e Ãguas naturais, com percentuais de recuperaÃÃo variando de 78,45 a 92,13%. Nas metodologias desenvolvidas, foram obtidos baixos valores de LD e de LQ, recuperaÃÃo entre 78,00-130,0% e precisÃo intermediÃria com RSD < 5,00%, mostrando que estas metodologias apresentam Ãtima sensibilidade, eficiÃncia e precisÃo. / The present work describes the electrochemical behavior of the antibiotic cefuroxime (CFX) and cephalexin (CFA) by cyclic voltammetry (CV) and the development of an electroanalytical methodology for CFX and CFA determination on mercury electrodes allied to the square wave voltammetry (SWV). In this work, CFX showed two irreversible reduction peak at -0.35 V (peak 1) and -1.03 V (peak 2), with the participation of two electrons and two protons for both peaks. It is suggested that the reduction reaction of the CFX occurs on the group â C = N â for the peak one and on the group â CH2 â R for the peak two. Under optimized conditions, the results were obtained in BR buffer pH 2.0, f = 90 s-1, a = 30 mV and &#916;Es = 2 mV. Considering the peak 1, analytical curves were constructed and the limits of detection (LOD) and quantitation (LOQ) were calculated with LOD = 4.92Ã10-9mol L-1and LOQ = 1.64Ã10-8mol L-1. The recovery in electrolyte was 109.15% with RSD = 2.39% (n = 3). The methodology was applied in raw natural waters, commercial formulations and bovine milk obtaining recovery values from 96.40 to 129.4%. CFA reductions waves are observed at -0.97 V (peak 1) and -1.2 V (peak 2). These reduction waves are attributed to the reduction of ethylenic bond of CFA involving the transfer of two electrons and two protons. The optimized conditions were obtained in BR buffer pH 2.0, f = 100 s-1, a = 30 mV and &#916;Es = 4 mV. Considering the peak at -1.2 V, analytical curves were constructed and were calculated with LOD = 1.27Ã10-8mol L-1and LOQ = 4.23Ã10-8 mol L-1. The recovery in electrolyte was 89.19% with RSD = 1.51% (n = 3). The methodology was applied to quantify in raw natural waters, commercial formulations and bovine milk obtaining recovery values from 78.45 to 92.13%. In developed methodologies, we obtained low values of LOD and LOQ, recovery between 78.00 to 130.00% and reproducibility below 5.00%, showing that those methods had excellent sensitivity, precision and efficiency.

A circulação extracorpórea com hipotermia (CEC-H) é um procedimento comumente utilizado em cirurgias cardíacas, que representa um fator de risco para o paciente por promover extensa hemodiluição e profundas alterações fisiológicas. Nestas cirurgias, utiliza-se a cefuroxima como antimicrobiano para profilaxia de infecções, estando sua concentração inibitória mínima (CIM90) na faixa de 4 a 16 &#181;g/mL dependendo da espécie e cepa bacteriana. Vários esquemas posológicos tem sido propostos para a profilaxia com este antimicrobiano. Assim, o objetivo do presente estudo foi investigar a farmacocinética e a disponibilidade sistêmica da cefuroxima, administrada I.V., bolus, na dose de 1,5g a 17 pacientes submetidos à cirurgia cardíaca com ou sem CEC-H. Desenvolveu-se método analítico simples seletivo e sensível em CLAE-UV para determinar a cefuroxima no plasma e tecido subcutâneo destes pacientes. Os resultados evidenciaram que independente das alterações causadas pela CEC-H, obtiveram-se baixas concentrações plasmáticas, inferiores ao CIM90, a partir da 9a hora após a administração da medicação nos dois grupos de pacientes investigados. Esta baixa disponibilidade sistêmica da cefuroxima após administração de 1,5 g pode favorecer o desenvolvimento de infecções pós-cirúrgicas e o desenvolvimento de cepas bacterianas resistentes. Por outro lado, a disposição cinética da cefuroxima foi alterada pela CEC-H, evidenciando-se ligeiro mas significativo prolongamento da meia vida biológica e redução da depuração plasmática nos pacientes submetidos a este procedimento. A ausência de alterações no volume de distribuição está de acordo com a penetração do antibiótico no tecido, uma vez que a quantidade de cefuroxima presente no subcutâneo foi comparável em ambos os grupos de pacientes investigados. Os dados obtidos permitem recomendar mudanças no regime posológico para manter níveis plasmáticos adequados e garantir a profilaxia com cefuroxima. / Cardiopulmonary bypass and hypothermia (HCPB) is a procedure commonly used during heart surgery, representing a risk factor for the patient by promoting extensive hemodilution and profound physiological changes. Cefuroxime is used for the prophylaxis of infection after heart surgery and its minimum inhibitory concentration (MIC90) may vary from 4 to 16 &#181;g/mL depending on the bacterial species and strain. Several dose schemes have been suggested for prophylaxis with this antimicrobial agent. Thus, the objective of the present study was to assess in a comparative manner the systemic availability of cefuroxime administered intravascularly at the dose of 1.5 g in bolus to 17 patients submitted to heart surgery with or without HCPB. An improved, simple, selective and sensitive micromethod based on HPLC-UV is described to determine cefuroxime in plasma and fat tissue. Despite the differences recorded during the study period as a consequence of HCPB, antibiotic concentrations lower than MIC90 were obtained as early as after the 9th h for the surgical patients of the two groups of patients investigated. Thus, the low systemic availability of cefuroxime after the administration of a 1.5 g dose may be the factor responsible for postoperative infections and may favor the development of resistant bacterial strains. By the other hand, cefuroxime kinetic disposition was altered by HCPB showing a slight prolongation of biological half-life e reduction of plasma clearance. Unchanged apparent volume of distribution was according antibiotic tissue penetration since in both groups of patients the amount of cefuroxime obtained was comparable. The data obtained permit us to recommend a change in the dose scheme in order to maintain adequate plasma levels of the drug and thus guarantee prophylaxis with cefuroxime.

<p>Serum amyloid A protein (SAA) is an acute phase protein that has recently gained increasing interest as a potential marker for disease and treatment monitoring. We investigated SAA and CRP levels in (a) patients with various common infectious diseases (n=98), (b) patients with pyelonephritis (n=37) versus patients with cystitis (n=32), (c) healthy individuals of varying ages (n=231), (d) very immature newborn infants with or without nosocomial infections (NIs) (n=72) and (e) patients with bacterial infections treated with cefuroxime (n=81). </p><p>SAA significantly correlated with CRP in viral as well as in bacterial infections (for the total group: r²=0.757, p<0.0001) and showed a systemic inflammatory response in 90% of the patients with cystitis as compared with 23% for CRP. Equally high efficiencies (0.96 and 0.94 for SAA and CRP, respectively) were observed in discriminating between pyelonephritis and cystitis. SAA and high sensitive (hs) CRP were lower in umbilical cords (p<0.0001) and higher in elderly adults (p<0.0001-0.03) than in the other age groups; higher in immature newborn infants than in term infants; and higher in the NI group than in the non-NI group. Interindividual variabilities of the time course of the biomarkers SAA and CRP were considerable. Because of the smoothed distribution of SAA and CRP (i.e. elevations were both essentially unchanged during the first 3 days of cefuroxime treatment), these markers were not useful when deciding parenteral-oral switch of therapy, which occurred within this time period in most cases.</p><p>SAA is a sensitive systemic marker in cystitis. SAA and hsCRP in umbilical cord blood are close to the detection limit and increase with age. They increase in relation to NI in very immature newborn infants and might therefore be used in diagnosis and monitoring. Finally, SAA and CRP in adults with bacterial infections could not predict an early parenteral-oral switch of antimicrobial therapy.</p>

Serum amyloid A protein (SAA) is an acute phase protein that has recently gained increasing interest as a potential marker for disease and treatment monitoring. We investigated SAA and CRP levels in (a) patients with various common infectious diseases (n=98), (b) patients with pyelonephritis (n=37) versus patients with cystitis (n=32), (c) healthy individuals of varying ages (n=231), (d) very immature newborn infants with or without nosocomial infections (NIs) (n=72) and (e) patients with bacterial infections treated with cefuroxime (n=81). SAA significantly correlated with CRP in viral as well as in bacterial infections (for the total group: r2=0.757, p&lt;0.0001) and showed a systemic inflammatory response in 90% of the patients with cystitis as compared with 23% for CRP. Equally high efficiencies (0.96 and 0.94 for SAA and CRP, respectively) were observed in discriminating between pyelonephritis and cystitis. SAA and high sensitive (hs) CRP were lower in umbilical cords (p&lt;0.0001) and higher in elderly adults (p&lt;0.0001-0.03) than in the other age groups; higher in immature newborn infants than in term infants; and higher in the NI group than in the non-NI group. Interindividual variabilities of the time course of the biomarkers SAA and CRP were considerable. Because of the smoothed distribution of SAA and CRP (i.e. elevations were both essentially unchanged during the first 3 days of cefuroxime treatment), these markers were not useful when deciding parenteral-oral switch of therapy, which occurred within this time period in most cases. SAA is a sensitive systemic marker in cystitis. SAA and hsCRP in umbilical cord blood are close to the detection limit and increase with age. They increase in relation to NI in very immature newborn infants and might therefore be used in diagnosis and monitoring. Finally, SAA and CRP in adults with bacterial infections could not predict an early parenteral-oral switch of antimicrobial therapy.

A circulação extracorpórea com hipotermia (CEC-H) é um procedimento comumente utilizado em cirurgias cardíacas, que representa um fator de risco para o paciente por promover extensa hemodiluição e profundas alterações fisiológicas. Nestas cirurgias, utiliza-se a cefuroxima como antimicrobiano para profilaxia de infecções, estando sua concentração inibitória mínima (CIM90) na faixa de 4 a 16 &#181;g/mL dependendo da espécie e cepa bacteriana. Vários esquemas posológicos tem sido propostos para a profilaxia com este antimicrobiano. Assim, o objetivo do presente estudo foi investigar a farmacocinética e a disponibilidade sistêmica da cefuroxima, administrada I.V., bolus, na dose de 1,5g a 17 pacientes submetidos à cirurgia cardíaca com ou sem CEC-H. Desenvolveu-se método analítico simples seletivo e sensível em CLAE-UV para determinar a cefuroxima no plasma e tecido subcutâneo destes pacientes. Os resultados evidenciaram que independente das alterações causadas pela CEC-H, obtiveram-se baixas concentrações plasmáticas, inferiores ao CIM90, a partir da 9a hora após a administração da medicação nos dois grupos de pacientes investigados. Esta baixa disponibilidade sistêmica da cefuroxima após administração de 1,5 g pode favorecer o desenvolvimento de infecções pós-cirúrgicas e o desenvolvimento de cepas bacterianas resistentes. Por outro lado, a disposição cinética da cefuroxima foi alterada pela CEC-H, evidenciando-se ligeiro mas significativo prolongamento da meia vida biológica e redução da depuração plasmática nos pacientes submetidos a este procedimento. A ausência de alterações no volume de distribuição está de acordo com a penetração do antibiótico no tecido, uma vez que a quantidade de cefuroxima presente no subcutâneo foi comparável em ambos os grupos de pacientes investigados. Os dados obtidos permitem recomendar mudanças no regime posológico para manter níveis plasmáticos adequados e garantir a profilaxia com cefuroxima. / Cardiopulmonary bypass and hypothermia (HCPB) is a procedure commonly used during heart surgery, representing a risk factor for the patient by promoting extensive hemodilution and profound physiological changes. Cefuroxime is used for the prophylaxis of infection after heart surgery and its minimum inhibitory concentration (MIC90) may vary from 4 to 16 &#181;g/mL depending on the bacterial species and strain. Several dose schemes have been suggested for prophylaxis with this antimicrobial agent. Thus, the objective of the present study was to assess in a comparative manner the systemic availability of cefuroxime administered intravascularly at the dose of 1.5 g in bolus to 17 patients submitted to heart surgery with or without HCPB. An improved, simple, selective and sensitive micromethod based on HPLC-UV is described to determine cefuroxime in plasma and fat tissue. Despite the differences recorded during the study period as a consequence of HCPB, antibiotic concentrations lower than MIC90 were obtained as early as after the 9th h for the surgical patients of the two groups of patients investigated. Thus, the low systemic availability of cefuroxime after the administration of a 1.5 g dose may be the factor responsible for postoperative infections and may favor the development of resistant bacterial strains. By the other hand, cefuroxime kinetic disposition was altered by HCPB showing a slight prolongation of biological half-life e reduction of plasma clearance. Unchanged apparent volume of distribution was according antibiotic tissue penetration since in both groups of patients the amount of cefuroxime obtained was comparable. The data obtained permit us to recommend a change in the dose scheme in order to maintain adequate plasma levels of the drug and thus guarantee prophylaxis with cefuroxime.

<p>Uprkos op&scaron;te prihvaćenom stavu da u trudnoći lekove treba izbegavati, veliki broj trudnica tokom trudnoće uzima lekove sa manje ili vi&scaron;e opravdanja. Primena lekova u trudnoći zahteva dodatnu patnju, jer se mora voditi računa o zdravlju majke i zdravlju jo&scaron; nerođenog&nbsp; deteta. Većina lekova koji nalaze primenu u trudnoći, nisu ispitani u kontrolisanim studijama na trudnicama, već se njihov uticaj naljudski fetus, bazira na predpostavkama i kliničkim istraživanjima na životinjama. Odsustvo studija dovodi do toga da se trudnicama obično prepisuju lekovi u dozi za odrasle osobe, koje ne prate fiziolo&scaron;ke promene u trudnoći. Tokom trudnoće u telu trudnica dolazi do promena u funkciji organa i organskih sistema, a zbog nastalih promena menja se i sudbina leka u organizmu. Sistemske bolesti trudnice poput hipertenzije i dijabetesa dovode do hemodinamskih promena i utiču na nastanak patolo&scaron;kih promena posteljice, &scaron;to sve zajedno menja farmakokinetiku lekova i njihov transplacentrarni transport. Ukupno 75 trudnica je uključeno u studiju i podeljeno u tri grupe: zdrave trudnice-kontrolna grupa (n=31), trudnice sa hipertenzijom (n=30) i trudnice sa dijabetesom (n=14). Sve trudnice su u premedikaciji primile iste lekove koji su deo standardne kliničke&nbsp; procedure. Trudnice su primile jednu dozu diazepama intramuskularnom injekcijom (10mg/2ml), a intravenski su primile pojedinačne doze cefuroksima (1,5g), metoklopramida (10mg/2ml) i ranitidina (50mg/2ml). Od svakog para majka-dete ukupno je analizirano po 5 uzoraka. Uzorci krvi od majke uzimani su u tri vremenske tačke: nakon davanja leka, u momentu ekstrakcije deteta i nakon porođaja. Uzorci&nbsp; krvi&nbsp; deteta&nbsp; uzimani su&nbsp; nakon&nbsp; porođaja iz pupčane vene i arterije. Prikupljeni uzorci plazme analizirani su metodom tečne hromatografije visokih performansi (HPLC). Istraživanje je pokazalo da lekovi&nbsp; primenjeni u premedikaciji&nbsp; carskog reza prolaze transplacentarnu membranu i da se ni jedan&nbsp; od&nbsp; lekova&nbsp; primenjenih&nbsp; u studiji nije akumulirao u fetusu i nije imao neželjeno dejsvo na novorođenče. Cefuroksim, ranitidin i metoklopramid pokazali su nizak feto-maternalni transfer, dok je diazepam pokazao visok&nbsp; feto-maternalni transfer. Izmerene koncentracije cefuroksima u plazmi trudnica u momentu porođaja bile su &ge;8 &mu;g/ml, &scaron;to je koncentracija veća od MIC za većinu patogena odgovornih za nastavak infekcija u aku&scaron;erstvu. Koncentracije cefuroksima u fetalnoj plazmi bile su &ge;4&mu;g/ml &scaron;to je veće od&nbsp; MIC koncentracija za veliki broj patogena. Gestacijska starost trudnoće nije uticala na obim prolaska cefuroksima&nbsp; kroz placentu, koji je prolazi uglavnom pasivnom difuzijom. Farmakokinetski parametri cefuroksima razlikovali su se kod hipertenzivnih i dijabetičnih trudnica, u odnosu kontrolnu grupu, ali ove bolesti nisu imale značajan uticaj na smanjenje terapijske efikasnosti cefuroksima. Farmakokinetika cefuroksima kod hipertenzivnih&nbsp; trudnica&nbsp; ukazala je na bržu eliminaciju cefuroksima iz krvi majke i na veću distribuciju leka u okolna tkiva. U dijabetičnoj grupi trudnica i novorođenčadi koncentracije cefuroksima su bile vi&scaron;e u odnosu na druge ispitivane grupe, dok je feto-maternalni odnos bio niži, &scaron;to ukazuje na postojanje strukturalne i funkcionalne pomenu posteljice u dijabetesu. Hipertenzija i dijabetes trudnica nisu imali uticaj na prodor ranitidina kroz placentu. Hipertenzija i dijabetes trudnica nisu uticali na većinu farmakokinetskih parametara ranitidina, mada je zabeleženo smanjenje volumena distribucije u ovim grupama trudnica, &scaron;to bi moglo da ukazuje na njihovu hemodinamsku nestabilnost i povećanje slobodne frakcije ranitidina. Koncentracija metoklopramida bila veća u krvi majki u odnosu na krv fetusa. Transport metoklopramida iz fetusa ka majci bio je dominantniji, a naročito u hipertenzivnoj i dijabetičnoj grupi trudnica. Hipertenzija i dijabetes trudnica uticali su na zadržavanje metoklopramida u fetusu. Koncentracije dijazepama u majčinoj i fetalnoj krvi bile su vi&scaron;e u kontrolnoj i hipertenzivnoj grupi trudnica. Hipertenzija i dijabetes trudnica povećavaju&nbsp; transfer diazepama kroz placentu, povećanjem koncentracije slobodnih masnih kiselina, steroidnih hormona, smanjenjem vezivnog kapaciteta potencijalna opasnost od neželjenog dejstva diazepama i njegovih metabolita na fetus i novorođenče. Ova doktorska studija ukazuju na potrebu obimnijih farmakokinetskih istraživanja kako na zdravim tako i na bolesnim trudnicama, koja će dati zaključke utvrđene na dokazima i pomoći u individualnom terapijskom pristupu svakoj trudnici.</p> / <p>In spite of&nbsp; the widespread opinion&nbsp; that&nbsp; drugs should be avoided in pregnancy, a great number of&nbsp; pregnant&nbsp; women&nbsp; take drugs with more or less justification.&nbsp; Administration of drugs in pregnancy requires additional attention because the health of&nbsp; both the mother and&nbsp; her unborn child must be protected. Majority of drugs administered in pregnancy have not been tested&nbsp; within the controlled studies performed on pregnant women, but&nbsp; their effect on the human foetus is based on assumptions and clinical trials performed on animals. This absence of studies results in the situation that pregnant&nbsp; women are usually prescribed drugs in a dose&nbsp; for adults, which does not take into account the physiological changes happening in pregnancy. During pregnancy, the pregnant woman&rsquo;s body undergoes changes in the<br />functions of organs and organ systems. These changes further affect the destiny of a&nbsp; drug in the organism. In pregnant women, systemic diseases such as hypertension&nbsp;&nbsp; and diabetes mellitus lead to hemodynamic changes and cause pathological&nbsp; changes in placenta, thus changing the pharmacokinetics of drugs and their transplacental transport. The study sample consisted of 75 pregnant women, who were divided into three groups as follows: the control group included healthy pregnant&nbsp; women (n=31), a group of pregnant women&nbsp; with&nbsp; hypertension (n=30) and&nbsp; a group of&nbsp; those&nbsp; with&nbsp; diabetes mellitus (n=14). All of them were administered the same drugs as a part of standard clinical procedure in premedication. The pregnant women received a single dose of diazepam by intramuscular injection (10mg/ml), and individual doses of cefuroxime (1.5mg), metoclopramide (10mg/2ml) and ranitidine (50mg/2ml). Five samples taken from each mother-infant pair were analyzed. Blood samples were taken from the mother three times: after drug administration, at the moment of extraction of baby and after delivery. Baby&rsquo;s blood samples were taken from the umbilical cord vein and artery after delivery. Plasma samples were analyzed by the method of high-performance liquid chromatography (HPLC). The research has shown that drugs administered in premedication of caesarean section went through the transplacental membrane and that none of the tested drugs accumulated in the foetus and had an adverse effect on the newborn. Cefuroxime, ranitidine and metoclopramide were shown to have a low transfer between the mother and her foetus, whereas diazepam showed a high foetal-maternal transfer. Cefuroxime concentrations measured in the pregnant woman&rsquo;s and foetal plasma at the moment of delivery were &ge;8&mu;g/ml and &ge;4&mu;g/ml, respectively, that&nbsp; being above the minimum inhibitory concentration (MIC) for most pathogens responsible for the development of infection in obstetrics. Gestational age had no effect on the range of cefuroxime flow through the placenta, which happens mostly by&nbsp; passive diffusion. Pharmacokinetic parameters of cefuroxime differed in the pregnant&nbsp; women having hypertension and diabetes mellitus from the controls; however, these diseases did not significantly reduce the therapeutic efficacy of cefuroxime. Pharmacokinetics of cefuroxime indicated faster elimination of&nbsp; cefuroxime into the maternal blood and greater distribution of the drug into the surrounding tissues in the hypertensive pregnant women. In the group consisting of pregnant women and newborns having diabetes, the cefuroxime concentrations were higher than in other groups, whereas foetal-maternal relation was lower, which suggests the presence of structural and functional change in the placenta in diabetes. Hypertension and diabetes mellitus had no affect either on the flow of ranitidine through the placenta in the pregnant women or on&nbsp; the&nbsp; majority of pharmacokinetic parameters of ranitidine, although a certain reduction in the volume&nbsp; of distribution was recorded in these groups of pregnant women, which could suggest their hemodynamic instability and increased free fractions of ranitidine. The concentration of metocloporamide was higher in the maternal blood than in the&nbsp; foetal blood, and&nbsp; the transport of metocloporamide from the foetus towards the mother was more dominant, particularly in&nbsp; the&nbsp; group of&nbsp; hypertensive and diabetic&nbsp;&nbsp;&nbsp; pregnant women. Metoclopramide tended to retain in the foetuses of mothers having&nbsp; hypertension and diabetes. The concentrations of diazepam in maternal and foetal blood were higher in the controls&nbsp; and hypertensive&nbsp; pregnant&nbsp; women. Hypertension and diabetes in pregnant&nbsp; women increase the transfer of diazepam through the placenta by increasing the concentration of free fatty acids and steroid hormones and by reducing the binding capacity of carrier proteins and the concentration of plasma&nbsp;&nbsp; proteins, thus increasing the potential danger of adverse effects of diazepam and its metabolites on the foetus and the newborn. This doctoral study suggests the necessity for more extensive pharmacokinetic research including both healthy and affected pregnant women that would lead to conclusions based on evidence and help to develop individual therapeutic approach to each pregnant woman.</p>