[Measurement of rifampicin concentrations in tuberculous pleural effusion before and after combination treatment with oral and local rifampicin].

Objective: To investigate the changes of rifampin concentrations in pleural effusion before and after combination treatment with oral and pleural administration of rifampicin by electro-phonophoresis(EP). Methods: A self-control study was performed in 32 cases of tuberculous pleurisy treated in the Second Department of Respiratory Medicine of Affiliated Hospital of Zunyi Medical College between September 2016 and January 2018. Based on the weight of each patient, an oral administration of isoniazid (0.3-0.4 g/d), rifampicin (0.45-0.60 g/d),ethambutol(0.75 g/d),and pyrazinamide (1.0-1.5 g/d) were given. After a 5-day traditional anti-tuberculosis treatment, an additional EP treatment was applied by penetrating chest wall to deliver 3 ml of rifampicin. The concentration of rifampicin in 5 ml pleural effusion was measured at 0, 0.5, 1, 2, 4 and 8h after applying EP treatment using high performance liquid chromatography. The measurement data were analyzed by using statistic software SPSS 20.0. The results were expressed by x±s and t test was conducted, with a statistical significance of P<0.05. Results: The average concentration of rifampicin in pleural effusion was (2.2±1.1) µg/ml by oral rifampicin alone. The concentration of rifampicin was (2.7±1.1) µg/ml, (3.0±1.4) µg/ml, (3.2±1.2) µg/ml, (2.8±1.2) µg/ml and (1.3±1.1) µg/ml, respectively, at 0.5 h, 1, 2, 4, 8 h after combining local EP treatment. The results indicated that combining local EP treatment significantly increased the drug concentration in pleural effusion, which lasted for about 5 hours. Conclusions: By applying rifampicin into pleural cavity through EP treatment with penetration of the chest wall, the concentration of rifampicin in pleural effusion of patients with tuberculous pleurisy could be increased. Combined with oral administration of rifampicin, this treatment could prolong the effective drug concentration in pleural effusion, which was beneficial to the bactericidal effects of rifampicin.

Disposition of fenbendazole in the rabbit.

The disposition of fenbendazole was studied in rabbits following either oral or intravenous administration. The major metabolites appearing in plasma were fenbendazole sulphoxide (oxfendazole) and fenbendazole sulphone. Calculation of the total urinary and faecal elimination of the drug and of its known metabolites showed that only 40 per cent of the dose was recovered after oral dosing; 29.7 per cent after an intravenous dose. The sulphoxide and sulphone were minor elimination products. The major excretory metabolite was p-hydroxyfenbendazole.

Disposition of fenbendazole in cattle.

Fenbendazole (FBZ) was administered to cattle IV and orally in a crossover design. Plasma concentration vs time profiles were reported for FBZ and its major metabolites, the sulfoxide (oxfendazole) and the sulfone. The total excretion of FBZ and its metabolites in urine and feces was also measured for 6 days after administration. All known metabolites were identified in urine and feces except for fenbendazole amine. Neither this minor metabolite nor p-hydroxyfenbendazole (FBZ-OH) appeared in plasma. The major excretory product was FBZ-OH. After oral administration, only 44.6% of the dose was eliminated after 6 days, indicating a fairly high degree of sequestration, probably within the gastrointestinal tract.

Disposition of fenbendazole in the goat.

The disposition of fenbendazole was studied in goats after oral or IV administration. Plasma concentration vs time profiles were determined for fenbendazole and all of its metabolites. The total excretion of the drug and its metabolites in urine and feces was also measured for 6 days. A biliary cannula was inserted in 1 goat to study the excretion of fenbendazole and its metabolites into the bile. Fenbendazole was converted to its sulfoxide (oxfendazole), and the sulfone, primary amine, and p-hydroxylated metabolites. The active metabolite, oxfendazole, appeared in plasma, but only trace amounts were found in feces or urine. The major excretory metabolite was p-hydroxyfenbendazole.

Comparison of hepatic drug metabolizing enzyme activities in several agricultural species.

1. Several pathways of drug metabolizing enzyme activity were measured in hepatic fractions of cattle, sheep, goats, chickens, turkeys, ducks, rabbits and rats. The pathways examined included the O-demethylation of p-nitrophenol, microsomal ester hydrolysis of procaine and glucuronidation of p-nitrophenol, and the cytosolic acetylation of sulfamethazine and sulfation of 2-naphthol. 2. For most enzymatic pathways measured, goats were more similar to sheep (wether) than to cattle (steers). The exception was UDP-glucuronyltransferase activity, which was significantly higher for the goat than for any other species studied. 3. Within the avian subset, the chicken and turkey were usually the most similar species. 4. The activities of arylsulfotransferase isozymes III and IV were particularly low for the duck compared to the chicken and turkey. 5. N-acetyltransferase activity was very high for rabbits and very low for sheep and goats.