Browsing by Author "Guevara, A"

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    Pharmacokinetics and hepatotoxicity of diclofenac using an isolated perfused rat liver
    (EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER, 1997) GonzalezMartin, G; Dominguez, AR; Guevara, A
    Pharmacokinetics and hepatotoxicity of diclofenac was studied in a recirculating model of isolated perfused rat liver. Ten male Sprague-Dawley rat (weighing 230-330 g) livers were perfused for 2 h with 250 mt Krebs-Henseleit bicarbonate buffer that contained 10.75 mg (group A, a = 5) and 1.075 mg (group B, n = 5) of diclofenac (approximately 100 and 10 times the therapeutic dose in man, respectively). Samples were collected from the efflux at regular time intervals for the determination of diclofenac concentrations by a high performance liquid chromatography (HPLC) method. Pharmacokinetic analyses were carried out using a computer program. To establish viability of the liver and toxicity of the drug, enzyme activity measurements of lactate dehydrogenase (LDH), aspartate aminotransferase (SGOT) and piruvate aminotransferase (SGPT) were performed by a spectrophotometric method. Oxygen consumption was also recorded during the entire perfusion period. Both groups presented bicompartmental kinetics. Concentration profiles showed that group B had a better metabolizing capacity, reflected in a 85.54 +/- 37.05 min half-life, a 0.52 +/- 0.19 mt min(-1) g(-1) liver clearance and a 0.517 +/- 0.188 extraction ratio, compared to group A, which presented a 123.95 +/- 88.13 min half-life. a 0.1164 +/- 0.067 mt min(-1) g(-1) liver clearance (P < 0.002) and a 0.116 +/- 0.680 extraction ratio (P < 0.002). LDH activity showed a significant increase in group A at 90 min in comparison with the control group, while in group B this increase was significantly higher at 10 min (P < 0.004). The aminotransferase levels did not show a significant increase. According to these results, diclofenac would not have a direct hepatotoxic effect, even at doses 100 times higher than therapeutic ones.
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    Pharmacokinetics of vancomycin in patients with severely impaired renal function
    (DUSTRI-VERLAG DR KARL FEISTLE, 1996) GonzalezMartin, G; Acuna, V; Perez, C; Labarca, J; Guevara, A; Tagle, R
    The pharmacokinetics of 1 g dose of intravenous vancomycin was studied in 8 patients with severe renal failure. Serum vancomycin levels were determined by fluorescence polarization immunoassay. After single dose of vancomycin peak concentrations ranged from 37.8 mu g.ml(-1) to 109.3 mu g. ml(-1) (mean 64.9 +/- 21.7 mu g.ml(-1)). Vancomycin trough concentration 168h after administration of the antibiotic ranged from 2.23 mu g.ml(-1) to 11.42 mu g.ml(-1) (mean 6.55 +/- 2.8 mu g.ml(-1)). The data were analyzed using a PCNONLINE computer program, and in all patients a triexponential model described how concentrations decreased in time. Three-compartment parameters obtained from the 8 patients were t(1/2) alpha = 0.312 +/- 0.242 h, t(1/2) beta 6.012 +/- 5.36 h, and t(1/2) gamma = 131.0 +/- 46.7 h. Vd = 0.158 +/- 0.121 1.kg(-1), Vdss = 0.920 +/- 0.248 1.kg(-1) and total Cl = 0.10 +/- 0.049 1.h(-1) per kg of weight. Between 1.5% and 21.2% of the administered vancomycin dose was eliminated during hemodialysis. The dialysis clearance of vancomycin ranged from 50.6 ml.min(-1) to 76.8 ml.min(-1) (average: 62.4 +/- 10.4 ml.min(-1)). However, after dialysis plasma concentrations returned to pre-dialysis values. In accordance to our kinetic study 1 g of vancomycin given every 7 days is adequate treatment for methicillin-resistant Staphylococcus aureus infections in patients with severe renal failure whose creatinine clearance is lower than 10 ml.min(-1).