[Fundamental studies on aspoxicillin in the field of gynecology. Penetration of the drug into the genital organs and the dead space fluid. Antibacterial activity of the drug against various strains of clinical isolates].
A new semisynthetic penicillin aspoxicillin (ASPC, TA-058) has been evaluated in regard to distribution into the genital organs and the dead space fluid and also in regard to antibiotic activity against various strains clinically isolated in the field of gynecology. The pharmacokinetic studies were made by using two-compartment model on the data of concentration in ovary, oviduct, endometrium, myometrium, cervix uteri and portio vaginalis of the genital organs and in dead space fluid. The following results were obtained. After one shot intravenous administration of 2.0 g ASPC, no marked difference was observed in concentration pattern between peripheral vein and uterine artery. Half-lives were 1.8 hours and 3.5 hours, respectively. The concentrations in various tissues of genital organs reached to the maximum at 36.2-73.6 micrograms/g during 0.07-0.44 hour with half-life varied from 0.53 to 1.3 hours. Area under the curves (AUC) of various tissues were reached to 30-65% of that uterine artery. After 2.0 g administration of ASPC drip intravenously (d.i.v.; for 30 or 60 minutes), there are no remarkable difference on simulation curve of concentration between peripheral vein and uterine artery. The peak level of various tissues attained to 22.5-40.3 micrograms/g during 0.53-0.56 hours and AUC of their concentration achieved about 20-40% of that of uterine artery after intravenous drip infusion for 30 minutes. After intravenous drip infusion for 60 minutes, tissue level reached to the maximum during 1.01-1.82 hours with half-life of 0.65-1.4 hours and AUC of tissue concentration achieved about 20-57% of that of uterine artery. The concentration of the drug in dead space fluid was reached to the maximum at 3.1 hours after the administration and its half-life was 5.3 hours. The in vitro activities of ASPC against clinical isolates were examined. The values of MIC70 and MIC80 were ranged 0.35-5.1 micrograms/ml against S. aureus, S. epidermidis, E. faecalis and P. mirabilis, respectively. Against E. coli, the value of MIC70 was attained 2.9 micrograms/ml, however, the value of MIC80 was more than 100 micrograms/ml due to the two-peaked activity of this drug against the bacteria. AUC and duration time of various tissue concentration were scrutinized regarding to the value of MIC80 of ASPC against S. aureus, S. epidermidis, E. faecalis and P. mirabilis.(ABSTRACT TRUNCATED AT 400 WORDS)
D000658:Amoxicillin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology; D001419:Bacteria / Q000187:drug effects* / Q000302:isolation & purification; D001424:Bacterial Infections / Q000382:microbiology; D005260:Female; D005831:Genital Diseases, Female / Q000382:microbiology; D005836:Genitalia, Female / Q000378:metabolism*; D007263:Infusions, Parenteral; D007275:Injections, Intravenous; D008954:Models, Biological; D010403:Penicillin Resistance; D014018:Tissue Distribution
C037485:aspoxicillin; D000658:Amoxicillin