[Studies on concentrations in body fluids of 16-membered ring macrolide antibiotics upon oral administration to healthy volunteers. Effects of their metabolites on bioassay values].
Plasma and urinary antibiotic concentrations measured by 3 different bioassay methods were compared to each other in vitro, after oral administrations of rokitamycin (RKM) tablet, midecamycin acetate (MOM) tablet or josamycin (JM) tablet at a dose of a potency of 600 mg to each of nine healthy volunteers. Method I (RKM bioassay method) was an agar-well method using the agar medium described in the Minimum Requirements for Antibiotic Products of Japan (MRAPJ medium, pH 6.5), method II (MOM bioassay method) was an agar-well method using mycin-assay agar (pH 8.0) and method III (JM bioassay method) was an agar-well method using nutrient agar (pH 7.8). Micrococcus luteus ATCC 9341 was used as the test organism in all the assay method. With any of the bioassay methods tested, plasma concentrations of RKM were determined to be higher than those of MOM or JM. When the three different bioassay methods were compared, method II and III gave consistently higher values than method I for plasma concentrations of any of the drugs tested. These higher values obtained by method II and III appeared to be due to their inability to correctly assay potencies of metabolites of these antibiotics. Using in vitro assay method, potencies of metabolites were found to be estimated higher than they should when method II and III were used. Method I, on the other hand, determined relative potencies of these antibiotics and their metabolites correctly, reflecting differences in MIC values of original antibiotics and their metabolites. Method I, therefore, should be used as the method of preference to determine concentrations of these drugs in body fluids.
Suzuki
T
T
Pharmaceutical Research Laboratories, Toyo Jozo Co., Ltd.
Sakai
A
A
Morishita
M
M
Ishioka
T
T
Shimizu
K
K
D000284:Administration, Oral; D000328:Adult; D001681:Biological Assay; D006801:Humans; D007933:Leucomycins / Q000008:administration & dosage / Q000493:pharmacokinetics*; D008297:Male; D015644:Miocamycin / Q000031:analogs & derivatives*
D007933:Leucomycins; D015644:Miocamycin; C026483:midecamycin; C033383:rokitamycin