Journal of Antimicrobial Chemotherapy (1990) 26, Suppl. E, 47-51
Concentrations of cefpodoxime in plasma and tonsiilar tissue after a single oral dose of cefpodoxime proxetil P. Gehanno*, J. M. Andrews*, F. Idton*, E. Sultan' and B. Lenfanf'
Seventeen patients undergoing tonsillcctomy received cefpodoxime proxetil orally in a dose equivalent to lOOmg cefpodoxime 4, 7 or 12 h before operation. Plasma and tonsiilar tissue concentrations of cefpodoxime were assayed by a microbiological method. Tonsiilar tissue concentrations after 4 and 7 h were 0-24 and 0-09 mg/kg respectively—being 23% of the plasma concentration. The tonsiilar tissue concentration after 12 h was less than 0-06 mg/kg. As the MIC for Streptococcus pyogenes is less than 0O6 mg/1, cefpodoxime proxetil may be of value in acute tonsillitis.
Introduction
Cefpodoxime proxetil is a prodrug which undergoes rapid hydrolysis by non-specific esterases in the bowel wall to yield the free acid, cefpodoxime—a new cephalosporin. This compound is effective against a wide range of Gram-positive and Gram-negative organisms, though exceptions are Enterococcus faecalis and Pseudomonas aeruginosa (Utsui, Inoue & Mitsuhashi, 1987; Chin & Neu, 1988; Jones & Barry, 1988). After oral administration of the prodrug equivalent to 100 mg cefpodoxime, the peak plasma concentration of cefpodoxime is 1-37 mg/1 after 2-4 h; the mean elimination half-life is 2-1 h, and 30-50% of the administered dose is eliminated unchanged in the urine (Tremblay et 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). S. pyogenes is the bacterial pathogen most often associated with acute tonsillitis. As the MIC for this organism is less than 006mg/1, it was of interest to measure cefpodoxime concentrations in tonsiilar tissue following a single oral dose of the prodrug.
Patients and methods
Patients Patients of either sex, aged between 15 and 50 years, undergoing tonsillectomy, whose informed consent had been obtained, were given a single dose of 130 mg cefpodoxime proxetil equivalent to lOOmg cefpodoxime before operation, with time intervals until 47 03O5-7453/9O/26EO47 + 05 $02.00/0
1090 The British Society for Antimicrobial Chemotherapy
Downloaded from http://jac.oxfordjournals.org/ at University of Edinburgh on May 27, 2012
"ENT Department, Hopital Bichat, 46 rue Henri Huchard, 75018 Paris, France; Dudley Road Hospital, Birmingham B18 7QH, UK; 'Laboratoires Diamant, Puteaux, and dlnstitut Roussel Uclaf, 93230 Romainville, France
b
48
P. Gehanno et aL
Plasma and tonsillar samples
Following collection of 5 ml blood by venepuncture into a dry lithium heparin tube on ice, the drug tablet was taken with 150 ml water by fasting patients at a time suitable to allow the required interval before tissue sampling at operation. At operation, one whole tonsil was obtained, placed in a sterile bottle and frozen at — 70°C until assay. Synchronously, a second sample of 5 ml blood was obtained. The tubes containing the blood samples were centrifuged at +4°C and the resultant plasma was kept at — 70°C until assay. For the assay of cefpodoxime in plasma and tissue samples, tonsillar tissue was homogenized in an equal volume of phosphate buffer, following which the assay of cefpodoxime was performed on the supernatant. A standard agar diffusion microbiological method (R. Wise & J. M. Andrews, Roussel Uclaf, data on file) employing Providencia rettgeri (323 UC2) as indicator organism was used. Lower limit of sensitivity was 0-02 mg/1 for plasma samples, 0-06mg/kg for tissue samples, and the coefficient of variation
Concentrations of cefpodoxime in plasma and tonsiilar tissue after a single oral dose of cefpodoxime proxetil P. Gehanno*, J. M. Andrews*, F. Idton*, E. Sultan' and B. Lenfanf'
Seventeen patients undergoing tonsillcctomy received cefpodoxime proxetil orally in a dose equivalent to lOOmg cefpodoxime 4, 7 or 12 h before operation. Plasma and tonsiilar tissue concentrations of cefpodoxime were assayed by a microbiological method. Tonsiilar tissue concentrations after 4 and 7 h were 0-24 and 0-09 mg/kg respectively—being 23% of the plasma concentration. The tonsiilar tissue concentration after 12 h was less than 0-06 mg/kg. As the MIC for Streptococcus pyogenes is less than 0O6 mg/1, cefpodoxime proxetil may be of value in acute tonsillitis.
Introduction
Cefpodoxime proxetil is a prodrug which undergoes rapid hydrolysis by non-specific esterases in the bowel wall to yield the free acid, cefpodoxime—a new cephalosporin. This compound is effective against a wide range of Gram-positive and Gram-negative organisms, though exceptions are Enterococcus faecalis and Pseudomonas aeruginosa (Utsui, Inoue & Mitsuhashi, 1987; Chin & Neu, 1988; Jones & Barry, 1988). After oral administration of the prodrug equivalent to 100 mg cefpodoxime, the peak plasma concentration of cefpodoxime is 1-37 mg/1 after 2-4 h; the mean elimination half-life is 2-1 h, and 30-50% of the administered dose is eliminated unchanged in the urine (Tremblay et 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). S. pyogenes is the bacterial pathogen most often associated with acute tonsillitis. As the MIC for this organism is less than 006mg/1, it was of interest to measure cefpodoxime concentrations in tonsiilar tissue following a single oral dose of the prodrug.
Patients and methods
Patients Patients of either sex, aged between 15 and 50 years, undergoing tonsillectomy, whose informed consent had been obtained, were given a single dose of 130 mg cefpodoxime proxetil equivalent to lOOmg cefpodoxime before operation, with time intervals until 47 03O5-7453/9O/26EO47 + 05 $02.00/0
1090 The British Society for Antimicrobial Chemotherapy
Downloaded from http://jac.oxfordjournals.org/ at University of Edinburgh on May 27, 2012
"ENT Department, Hopital Bichat, 46 rue Henri Huchard, 75018 Paris, France; Dudley Road Hospital, Birmingham B18 7QH, UK; 'Laboratoires Diamant, Puteaux, and dlnstitut Roussel Uclaf, 93230 Romainville, France
b
48
P. Gehanno et aL
Plasma and tonsillar samples
Following collection of 5 ml blood by venepuncture into a dry lithium heparin tube on ice, the drug tablet was taken with 150 ml water by fasting patients at a time suitable to allow the required interval before tissue sampling at operation. At operation, one whole tonsil was obtained, placed in a sterile bottle and frozen at — 70°C until assay. Synchronously, a second sample of 5 ml blood was obtained. The tubes containing the blood samples were centrifuged at +4°C and the resultant plasma was kept at — 70°C until assay. For the assay of cefpodoxime in plasma and tissue samples, tonsillar tissue was homogenized in an equal volume of phosphate buffer, following which the assay of cefpodoxime was performed on the supernatant. A standard agar diffusion microbiological method (R. Wise & J. M. Andrews, Roussel Uclaf, data on file) employing Providencia rettgeri (323 UC2) as indicator organism was used. Lower limit of sensitivity was 0-02 mg/1 for plasma samples, 0-06mg/kg for tissue samples, and the coefficient of variation
