Journal of Antimicrobial Chemotherapy (1990) 26, Suppl. E, 35-40
Concentrations of cefpodoxime in plasma and lung tissue after a single oral dose of cefpodoxime proxetil L. Couraud', J. M. Andrews', H. Lecoeui-% E. Sultan' and B. Lenfant'
Eighteen patients undergoing thoracotomy for suspected pulmonary neoplasia were given 200 mg cefpodoxime equivalent by mouth, before operation. Plasma samples were obtained before dose administration, and plasma and lung tissue samples were obtained at the time of operation which was 3, 6 or 12 h after the dose. All samples were assayed for cefpodoxime. The mean ratios for lung tissue/plasma concentrations were similar between 3 and 12 h after dose, suggesting that equilibrium between plasma and lung tissue concentrations was reached within 3 h of medication. The mean concentrations of cefpodoxime in lung tissue were 0-63 ±0-16, 0-52±0-09 and (H9±0-02mg/kg at 3, 6 and 12 h after administration, respectively. These observations indicate good, rapid and sustained penetration into lung tissue in concentrations ;> the MIC*, for most common micro-organisms found in community-acquired pneumonia.
Introduction Cefpodoxime proxetil is a prodrug that undergoes rapid hydrolysis by non-specific esterases in the bowel wall to yield the free acid, cefpodoxime. This third generation cephalosporin is effective against a wide range of Gram-positive and Gram-negative bacteria, though exceptions are Enterococcus faecalis and Pseudomonas aeruginosa (Utsui, Inoue & Mitsuhashi, 1987; Chin & Neu, 1988; Jones & Barry, 1988). The compound is very active against those pathogens found most commonly in lower respiratory tract infections. After oral administration of two tablets of the prodrug, equivalent in total to 200 mg cefpodoxime, the peak plasma concentration of cefpodoxime is 2-6 mg/1, reached after 2-4 h; the mean elimination half-life is 21 h; and 30-50% of the administered dose is eliminated unchanged in the urine (Tremblay el al., 1990). Cefpodoxime is only weakly bound (40%) to plasma proteins (F. Bree, P. N'Guyen & J. P. Tillement, Roussel, data on file). No accumulation occurs after repeated doses up to 200 mg every 12 h for 14 days in healthy subjects (M. T. Borin & K. K. Forbes, Roussel, data on file). Thus, it was of interest to measure the concentration of cefpodoxime in plasma and lung tissue after a single oral dose of the prodrug, equivalent to 200 mg cefpodoxime. 35 0305-7453/90/26E035 + 06 S02.00/0
© 1990 The British Society for Antimicrobial Chemotherapy
Downloaded from http://jac.oxfordjournals.org/ at University of Saskatchewan on May 27, 2012
'Department of Thoracic Surgery, Xavier Arnozan Hospital, 33000 Pessac, France; Dept of Microbiology, Dudley Road Hospital, Birmingham B18 7QH, UK; 'Roussel Laboratories, 75006 Paris; 'Institut Roussel Uclaf, 93230 Romainville, France
b
36
L. Couraud et at
Patients and methods
Patients
Plasma and lung tissue samples
Blood samples (5 ml) were taken just before dosing and at the same time as lung tissue sampling, and placed in dry lithium heparin tubes kept in melting ice and subsequently centrifuged at +4°C. The resultant plasma was kept at — 70°C until assay. A fragment of about 5 g lung tissue was obtained at the pre-determined time during the operative procedure, placed in a sterile vial and frozen at — 70°C until assay. The timing of this sampling depended on the group to which each patient had been assigned. Assay of cefpodoxime Cefpodoxime in plasma and tissue was assayed using a standard agar diffusion microbiological method (R. Wise & J. M. Andrews, Roussel, data on file), the test organism being Providencia rettgeri (323 UC2). This method has a lower limit of sensitivity of 0-02 mg/1 for plasma and of 0-06 mg/kg for tissue samples, the coefficient of variation being
Concentrations of cefpodoxime in plasma and lung tissue after a single oral dose of cefpodoxime proxetil L. Couraud', J. M. Andrews', H. Lecoeui-% E. Sultan' and B. Lenfant'
Eighteen patients undergoing thoracotomy for suspected pulmonary neoplasia were given 200 mg cefpodoxime equivalent by mouth, before operation. Plasma samples were obtained before dose administration, and plasma and lung tissue samples were obtained at the time of operation which was 3, 6 or 12 h after the dose. All samples were assayed for cefpodoxime. The mean ratios for lung tissue/plasma concentrations were similar between 3 and 12 h after dose, suggesting that equilibrium between plasma and lung tissue concentrations was reached within 3 h of medication. The mean concentrations of cefpodoxime in lung tissue were 0-63 ±0-16, 0-52±0-09 and (H9±0-02mg/kg at 3, 6 and 12 h after administration, respectively. These observations indicate good, rapid and sustained penetration into lung tissue in concentrations ;> the MIC*, for most common micro-organisms found in community-acquired pneumonia.
Introduction Cefpodoxime proxetil is a prodrug that undergoes rapid hydrolysis by non-specific esterases in the bowel wall to yield the free acid, cefpodoxime. This third generation cephalosporin is effective against a wide range of Gram-positive and Gram-negative bacteria, though exceptions are Enterococcus faecalis and Pseudomonas aeruginosa (Utsui, Inoue & Mitsuhashi, 1987; Chin & Neu, 1988; Jones & Barry, 1988). The compound is very active against those pathogens found most commonly in lower respiratory tract infections. After oral administration of two tablets of the prodrug, equivalent in total to 200 mg cefpodoxime, the peak plasma concentration of cefpodoxime is 2-6 mg/1, reached after 2-4 h; the mean elimination half-life is 21 h; and 30-50% of the administered dose is eliminated unchanged in the urine (Tremblay el al., 1990). Cefpodoxime is only weakly bound (40%) to plasma proteins (F. Bree, P. N'Guyen & J. P. Tillement, Roussel, data on file). No accumulation occurs after repeated doses up to 200 mg every 12 h for 14 days in healthy subjects (M. T. Borin & K. K. Forbes, Roussel, data on file). Thus, it was of interest to measure the concentration of cefpodoxime in plasma and lung tissue after a single oral dose of the prodrug, equivalent to 200 mg cefpodoxime. 35 0305-7453/90/26E035 + 06 S02.00/0
© 1990 The British Society for Antimicrobial Chemotherapy
Downloaded from http://jac.oxfordjournals.org/ at University of Saskatchewan on May 27, 2012
'Department of Thoracic Surgery, Xavier Arnozan Hospital, 33000 Pessac, France; Dept of Microbiology, Dudley Road Hospital, Birmingham B18 7QH, UK; 'Roussel Laboratories, 75006 Paris; 'Institut Roussel Uclaf, 93230 Romainville, France
b
36
L. Couraud et at
Patients and methods
Patients
Plasma and lung tissue samples
Blood samples (5 ml) were taken just before dosing and at the same time as lung tissue sampling, and placed in dry lithium heparin tubes kept in melting ice and subsequently centrifuged at +4°C. The resultant plasma was kept at — 70°C until assay. A fragment of about 5 g lung tissue was obtained at the pre-determined time during the operative procedure, placed in a sterile vial and frozen at — 70°C until assay. The timing of this sampling depended on the group to which each patient had been assigned. Assay of cefpodoxime Cefpodoxime in plasma and tissue was assayed using a standard agar diffusion microbiological method (R. Wise & J. M. Andrews, Roussel, data on file), the test organism being Providencia rettgeri (323 UC2). This method has a lower limit of sensitivity of 0-02 mg/1 for plasma and of 0-06 mg/kg for tissue samples, the coefficient of variation being
