VOL. 34 S-2 CHEMOTH8RAPY 913

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VOL. 34 S-2 CHEMOTH8RAPY 913

914 CHEMOTHERAPY APR. 1986 Fig. 1 Chemical structure of T-2588 and T-2525 T- 2588 pivaloyloxymethyl (+ )- (6 R, 7 R)-7-[(Z)-2- (2-amino- 4-thiazolyl)-2-methox yiminoacetamido]-3-[( 5-methyl- 2H-tetrazol- 2 -yl) methyl]- 8 -oxo- 5 - thia- 1 -azabicyclo [4. 2. 0] oct-2-ene-2-carboxylate T- 2525 (+)-(6 R, 7 R)-7-[(Z)-2-(2-amino-4-thiazoly1)- 2-methox yim inoacetam ido]-3-[ (5-me th yl-2 H-tetrazol-2-yl) methyl]-8-oxo-5-thia-l-azabicyclo [4. 2. 0] oct-2-ene-2- carboxylic acid

VOL. 34 S-2 CHEMOTHERAPY 915

916 CHEMOTHERAPY APR, 1986

VOL. 34 5-2 CHEMOTHERAPY 917

918 CHEMOTHERAPY APR. 1986

VOL. 34 S-2 CHEMOTHERAPY 919

920 CHEMOTHERAPY APR. 10 14

Table 2 Clinical effects classified by duration Table 3 Clinical effects classified by daily dose

CHEMOTHERAPY APR. 19E16 Table 4 Clinical effects of T-2588 Table 5 Serum and tonsil concentrations of T-2525 (after single oral administration of T-2588 200mg) N.D.: Not determined

CHEMOTHERAPY Table 6 Serum and mucosa of maxillary sinus concentrations of T-2525 (after single Oral administratfok of T-2588 240mg) Table 7 Serum levels and middle ear mucosa levels of T-2588 in guinea-pig with acute otitis media after oral administration of 200mg/kg (n=4) Test organism: K Pneumoniae ATCC 10031 Method : Paper disc method Fig. 2 Serum levels and middle ear mucosa levels of T-2588 in guinea-pig with acute otitis media after oral administration of 200 mg/kg (n=4)

CLINICAL AND EXPERIMENTAL STUDY OF T-2588 IN OTORHINOLARYNGOLOGICAL INFECTION YUTAKA FUJIMAKI, SHOZO KAWAMURA and HARUHISA HORIKAWA Department of Otorhinolaryngology, Juntendo University School of Medicine HIROSHI WATANABE Department of Otorhinolaryngology, Taketani Hospital We had reported the clinical and fundamental study on the utility of a new cephem antibiotic, T-2588, in otorhinolaryngological infection. A hundred mg or 200 mg of T-2588 was administered orally three times a day. T-2588 was administered 7 cases of acute otitis media, 16 of acute exacerbation of chronic otitis media, 4 of acute paranasal sinusitis, 3 of acute exacerbation of chronic sinusitis, 21 of acute tonsillitis, 4 of acute pharyngolaryngitis, 4 of acute pharyngitis,, 3 of acute exacerbation of chronic tonsillitis and 4 of other infections. Clinical efficacy was tested, in these 66 cases. Clinical effectiveness of these infections were revealed as follows: acute otitis media: 86%, acute exacerbation of chronic otitis media: 50%, acute sinusitis: 75%, acute exacerbation of chronic sinusitis: 67%, acute tonsillitis: 100%, acute exacerbation of chronic tonsillitis: 100%, acute pharyngolaryngitis: 100%, acute pharyngitis: 100%. Side effects were observed in one case with diarrhea. No abnormality of laboratory data were detected. Faucal tonsil and maxillary sinus mucosal level of T-2588 were assayed. Transfer ratio of the drug from serum to these tissues were as follows, tonsil: 16.9 `88.0%, maxillary sinus mucosa: 32 `84. 5%. Middle ear mucosal level of the drug was also assayed using acute otitis media model of guinea pigs, and following data was detected. Middle ear mucosal level of the drug after 200 mg/kg administration showed 2.83 peg (peak value) at 60 minutes after administration and 0.76ƒÊg/g at 4 hours after administration.

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