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OBJECTIVE: To assess the pharmacokinetics of clarithromycin (CLR) and its effects on oral and nasal microbiota in healthy volunteers in an open, randomized, two-period crossover design. METHODS: A single 500 mg oral dose of CLR (Group 1: Merck; Group 2: Klaricid) was administered observing a 1-week interval between doses. Blood samples were collected from pre-dose to 24 h. Plasmatic concentrations of CLR were quantified by the LC-MS-MS method. Saliva and nasal mucosa swabs were obtained previously and after 1.33, 2, 6 and 12 h of drug administration. Pharmacokinetics and PK/PD (t > MIC, %t > MIC and AUC0-24/MIC ratio) parameters were estimated. The microorganism counts were obtained on different culture media. RESULTS: No statistically significant differences were observed between the two formulations (p > 0.05) regarding the pharmacokinetic parameters. Total microorganisms, staphylococci and streptococci counts did not show statistical differences (p > 0.05) between the two groups during each sampling time. Considering the microorganisms of each group, no statistically significant differences were found after drug administration, but all differed from pre-dose counts (p < 0.05). The observed t > MIC ranged from 14.45 h (+/- 1.69) to 1.19 h (+/- 2.17) considering MICs of 0.25 microg/ml and 2.0 microg/ml, respectively. There was no correlation between any t > MIC, %t > MIC or AUC0-24 and bacterial reduction (between 0- and 12-h periods). However, the profile of reduction of microorganisms in both saliva and nasal samples were compatible with high values of t > MIC verified for both clarithromycin formulations. CONCLUSION: Both formulations of clarithromycin had similar pharmacokinetics and efficacy.

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Plasma and salivary amoxicillin (AMO) concentrations were quantified following a single oral dose (875 mg) of two formulations of AMO (Amoxicillin-EMS Sigma Pharma and Amoxil BD 875 mg). In addition, the effect of amoxicillin against oral microorganisms was accessed. The open, randomized, two-period crossover study was carried out in 20 volunteers. Saliva and blood samples were collected at 0, 0.5, 1, 2, 4, 8 and 12 h after drug administration, and quantified using HPLC-ESI-MS and HPLC, respectively. Streptococci counts, anaerobe counts and total microorganism counts were obtained. No differences were observed between formulations (p > 0.05) in the plasma and salivary AMO concentrations and the pharmacokinetic parameters (C(max), t(max), AUC(0-8), and AUC(0-infinity)) also showed no statistically significant differences between formulations (p > 0.05). Microorganism counts for the two formulations at all sampling times did not differ (p > 0.05) but all microorganism counts at 60 min post-dose showed a significant decrease (p < 0.05). Amoxicillin was effective in reducing oral microorganism levels up to 12 h post-dose.

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OBJECTIVE: To compare the bioavailability of clarithromycin 500 mg tablets (Merck S.A Industrias Quimicas, Sao Paulo, SP, Brazil, used as test formulation) and Klaricid (Abbott Laboratórios do Brasil Ltda, Sao Paulo, SP, Brazil, used as reference formulation) in 24 healthy volunteers. MATERIAL AND METHODS: The study was conducted using an open, randomized, two-period crossover design with one-week interval between doses. Blood samples were collected at pre-dose, 0.33, 0.66, 1, 1.33, 1.66, 2, 2.5, 3, 4, 6, 8, 10, 12, 16, 20 and 24 hours after the administration. AUC was calculated by the trapezoidal rule extrapolation method. Cmax and tmax were compiled from the plasmatic concentration-time data. Analysis of variance was carried out using logarithmically transformed AUC(0-inf), AUC(0-24 h), Cmax and untransformed tmax. RESULTS: Intraindividual coefficient of variation (CV%) values were 14.25% and 12.62%, respectively for Cmax and AUC(0-24 h). The geometric mean values (+/- SD) for AUC(0-24 h) (microg x h/ml), AUC(0-inf) (microg x h/ml), and Cmax (microg/ml) for test medication were 18.56 (+/- 6.87), 18.8 (+/- 5.70) and 2.45 (+/- 0.88); the obtained values for reference medication were 18.29 (+/- 5.39), 19.10 (+/- 7.21) and 2.5 (+/- 0.69). 90% Cl for clarithromycin geometric mean of AUC(0-24 h), AUC(0-inf) and Cmax ratios (test/reference) were: 93.6-105.9%, 93.8-106.2% and 89- 103.2%. CCONCLUSION The test medication was considered bioequivalent to the reference medication based on the rate and extent of absorption.

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OBJECTIVE: To compare the bioavailability of amoxicillin 875 mg tablets (EMS Sigma Pharma used as test formulation) and Amoxil BD 875 mg tablets (GlaxoSmithKline used as reference formulation) in 26 healthy volunteers. MATERIAL AND METHODS: 26 healthy volunteers (13 males and 13 females) received each formulation in an open, 2 x 2 crossover, randomized study with seven days of washout period between doses. Plasma samples were obtained over a 12-hour interval after administration. Plasmatic amoxicillin concentrations were obtained by combined reversed-phase liquid chromatography and mass spectrometry with positive ion electrospray ionization using the select ion monitoring method. AUC was calculated by the trapezoidal rule extrapolation method. Cmax and tmax were compiled from the plasmatic concentration-time data. Analysis of variance was carried out using logarithmically transformed AUC0-inf, AUC0-12 h, Cmax and untransformed tmax. RESULTS: The mean values (+/- SD) for AUC0-12 h (microg x h x ml(-1)), AUC0-inf (microg x h x ml(-1)), Cmax (microg x ml(-1)), t1/2 (h) and tmax (h), were, respectively: 55.42 (+/- 16.85), 55.42 (+/- 16.85), 18.59 (+/- 6.3), 1.49 (+/- 1.57) and 2.04 (+/- 0.75) concerning the test formulation, and 51.11 (+/- 18.9), 51.29 (+/- 19.12), 17.83 (+/- 5.86), 1.52 (+/- 1.31) and 2.02 (+/- 0.87) concerning the reference formulation. Confidence intervals (90%) of amoxicillin means of AUC0-12 h and Cmax ratios (test/reference) were: 0.961-1.149 and 0.914-1.142, respectively, agreeing with the bioequivalence criteria established by the Brazilian National Health Surveillance Agency. CONCLUSION: Both formulations were bioequivalent based on both the rate and extent of absorption.

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O tratamento das doenças respiratórias requerem a utilização de antibióticos, corticosteróides e broncodilatadores. Todavia é desejável que, na pediatria, estas medicações sejam restritas e se utilize uma via de administração confortável. O objetivo deste trabalho foi avaliar a utilização dos medicamentos do trato respiratório e antimicrobianos em pacientes pediátricos hospitalizados, por meio da análise de seus prontuários. Os dados foram coletados durante 120 dias, observando-se os medicamentos prescritos, as doses, as vias de administração e as medidas não farmacológicas prescritas. O critério de inclusão na pesquisa foi estar o paciente internado na pediatria, ter na prescrição um antimicrobiano ou medicamento para o trato respiratório. As análises dos 136 prontuários mostrou que 97,06% continham um antimicrobiano, sendo o mais prescrito ampicilina e o fenoterol e ipratrópio como broncodilatadores. Destaca-se que 21,35% das prescrições apresentaram dosagem abaixo do mínimo e em, 21,89% acima do máximo. Embora em 93,75% dos casos tenha havido prescrição de dieta por via oral, 70,59% dos pacientes tiveram prescrição de medicação por via intravenosa. Esses dados revelam o uso de doses subterapêuticas, prescrição excessiva de antimicrobianos e o uso freqüente da via parenteral que encarecem o tratamento, predispõem ao aparecimento de efeitos indesejáveis como superinfecção, prolongando o tempo de permanência no hospital

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The bioavailability of two suspension formulations of potassium diclofenac (Flogan, Merck and Cataflam, Ciba-Geigy) were compared in eighteen healthy male volunteers who received a single dose of 7 ml of each suspension (equivalent to 105 mg of potassium diclofenac) in an open randomized two period crossover design, with a fourteen-day washout period between doses. Serum samples were obtained over a 24 hour interval and diclofenac concentrations were determined by HPLC with ultraviolet detection. From the serum diclofenac concentration vs time curves, AUC[0-24] (area under the concentration vs time curves from 0-24 h), Cmax (maximum achieved concentration), Tmax (time to achieve Cmax) and Ke (terminal first order elimination constant) were obtained. Overlapping of Tmax intervals for both formulations was observed, but the important inter-subject variation observed in Cmax ratios did not allow equivalence conclusion for the rate of absorption. Equivalence in the extent of bioavailability between both potassium diclofenac suspension brands was concluded from the analysis of AUC[0-24] ratios.

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With the objective to evaluate the zinc needs of children submitted to rehydration and/or parenteral nutrition, the content of contaminating zinc was determined in intravenous solutions utilized at University Hospital of Ribeirão Preto, SP, Brazil. Zinc was measured in 40 bottles containing deionized water and submitted to the routine treatment for industrialization of serum for parenteral use, according to the standards of the University Hospital of Ribeirão Preto, Industrial Pharmacy. The effect of the sealing material employed (polished red stopper and unpolished black stopper) was observed, as well as time of contact between the solutions and rubber stoppers and latex slides, and the method of bottle conditioning (vertical or horizontal position) which permits contact of the solutions with the rubber stoppers. The gluco-saline solutions prepared in our Hospital and stored in glass bottles with unpolished black rubber stoppers and latex slide showed substantial zinc levels (1,220 to 4,860 micrograms/ml, n = 30). The same solutions kept in glass vials or plastic bottles were zinc free. The highest zinc levels were observed in the amino acid solutions placed in sealed bottles with unpolished black rubber stoppers (11,690 to 24,310 micrograms/ml, n = 20). It is important to be aware of these contaminating zinc levels to provide proper treatment involving this micronutrient.

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