Intestinal barrier function and serum concentrations of rifampin, isoniazid and pyrazinamide in patients with pulmonary tuberculosis

Intestinal barrier function and serum concentrations of rifampin, isoniazid and pyrazinamide were studied in healthy controls and patients with active pulmonary tuberculosis. A case-control study of 29 controls and 30 cases attending at the Health Center, July, 2004 to December, 2005 was conducted. The body mass index was significantly reduced in cases compared to controls (p < 0.001). The intestinal paracellular transport of lactulose was significantly (p = 0.019) reduced in cases compared to controls. The transcellular transport of mannitol and the lactulose:mannitol ratio were not significantly (p = 0.0698) reduced in cases compared to controls. Low serum concentrations of rifampin, isoniazid and pyrazinamide were observed in 81 percent (48/59), 92 percent (54/59) and 28 percent (12/59), respectively, in all individuals. The results demonstrated a marked decrease on intestinal paracellular transport in patients with active pulmonary tuberculosis and reduced serum concentrations of rifampin and isoniazid in both groups.

Determination of pyrazinamide in human by high performance liquid chromatography.

A facile and sensitive high performance liquid chromatographic (HPLC) technique has been developed for the determination pyrazinamide (PZA) in human plasma. Nicotinamide(NIA) is used as internal standard(IS). Plasma is deproteinized with 0.7 M perchloric acid; clear supernatant is neutralized with 1M NaOH and injected onto HPLC. The separation of pyrazinamide and the internal standard is carried out on a Supelco LC-18 (DB) column with a basic mobile phase. Pyrazinoic acid, the major metabolite, other anti-tuberculous drugs and endogenous components do not interfere with measurement of pyrazinamide. The limit of detection of pyrazinamide with this method is 0.2 mg/0.2 ml plasma (CV 8.2%).

Lack of effect of cimetidine and ranitidine on pyrazinamide kinetics in rats

Pyrazinamide [25 mgkg-1] kinetics was determined in cimetidine [40 mgkg-1] or ranitidine [50 mgkg-1] pretreated rats for seven days. animals received either 0.9% NaCl solution [control] or cimetidine or raintidine orally [5 mlkg-1]. Disposition of pyrazinamide was studied 24 h after the last does of pretreatment by injecting pyrazinamide [1 mlkg-1] into the tail vein. Blood samples [0.25ml] were drawn at 15.35.45 min. and 1.0, 1.5, 2.0, 3, 4, 5, 6 and 8h respectively after iv administration. Pyrazinamide plasma concentrations were analyzed using HPLC method. Cimetidine and ranitidine had no significant effect on volume of distribution [Vd], half life [t0.5], clearance [CL], mean residence times [MRT] and area under the curves [AUC] of pyrazinamide. These results suggest that cimetidine and ranitidine pretreatment does not affect significantly pyrazinamide kinetics in rats

Alteration in the levels of pyrazinamide in pleural fluid following simultaneous administration of prednisoline in patients of tubercular pleural effusion.

20 Patients of tuberculous pleural effusion were administered a combination of pyrazinamide (30 mg/kg) + isoniazid (300 mg) orally for 7 consecutive days and pyrazinamide was estimated by spectrophotometric method in serum and pleural fluid. Prednisolone was added to the above regimen for next 7 consecutive days and pyrazinamide was again estimated. The level of pyrazinamide in pleural fluid was 23.4 +/- 1.2 (micrograms/ml). Following addition of prednisolone the level increased (27.6 +/- 1.3) significantly (P less than 0.001). The serum pyrazinamide level was not influenced by simultaneous administration of prednisolone. The pleural fluid/serum pyrazinamide ratio was increased from 0.465 to 0.542 by the addition of prednisolone to therapeutic regimen.