各種抗菌剤の雄性性器内移行に関する基礎的研究

Abstract

ウィスター系雄ラット(体重300 g前後)を用い, 各種抗菌剤について雄性性器内濃度と, 血中, 肝および腎組織内濃度との関係を系統的に比較検討し, 加えてABPC筋注時のヒト前立腺組織内濃度を測定した.経口薬剤についてはABPC, CEX, EM, CP, NAおよびPA, 筋注および静注薬剤についてはABPC, CER, CEZ, EM, CPおよびGM (GM 1.6 mg/kg, その他の薬剤は20 mg/kg)を投与した.今回の成績をまとめると, 前立腺組織移行の良好なものは経口剤ではNAであり, 筋注および静注投与では血中濃度の比較的高いABPCおよびCERであった.CP, GMは全体的に雄性性器系臓器への移行が不良である.副睾丸組織への移行は, 投与方法および投与薬剤に関係なく睾丸より良好な値を示したが, 前立腺組織内移行にはおよばなかった.睾丸への移行はいずれの薬剤, 投与方法でも微量で, 精子形成という重要な機能を保護する, いわゆるBlood-Testis Barrierの存在を示唆していると思われた.今回の実験成績が, 男子性器系感染, たとえば前立腺炎に対する抗菌剤投与の目安になると思われる

The relationship between the concentrations of various antimicrobial agents in the genital organs of male rats, serum, liver and kidney after oral administration, intramuscular infusion and i.v. infusion were systematically compared and studied. The concentration of Ampicillin in human prostatic tissues after intramuscular infusion was also measured. The drug concentration in the prostatic tissues after oral administration of nalidixic acid (20 mg/kg) was highest 21.5 micrograms/g (2-hour value) which was about 4 times the serum level, followed by chloramphenicol, Cefalexin, Ampicillin, piromidic acid and erythromycin. The concentration of Ampicillin and Cefaloridine in the prostatic tissues after intramuscular infusion was high, but the concentration of Cefazolin, was low after both intramuscular infusion and i.v. infusion. The drug concentration in the prostatic tissues after i.v. infusion of Cefaloridine, Erythromycin, and Ampicillin was high. The concentration of Erythromycin was high only after i.v. infusion. The concentration of both Chloramphenicol and Gentamicin in the blood, and in the prostatic tissues were low. Of the drugs tested, the concentration of Ampicillin in human prostatic tissues was the highest being about 8 micrograms/g at 60 minutes after intramuscular infusion, which was about 40% of its concentration in the blood. The concentrations of antimicrobial agents in the epididymis and testis of the rats were low. Even the relatively high values were only about 10% of the concentration in the blood. The concentration of nalidixic acid in the prostatic tissues was 4 times as high as that of Piromidic acid. In summary, the antimicrobial agents showing high concentrations in the prostatic tissues were nalidixic acid by oral administration, Ampicillin and Cefaloridine by intramuscular infusion, and i.v. infusion, which showed relatively high concentrations in the blood. Irrespective of the route of administration, the concentrations of Chloramphenicol and Gentamicin in the male genitals were low. The drug concentration in the testis was very low irrespective of the chemotherapeutic and administration form. This seems to signify the presence of the so-called blood-testis barrier to protect the important function of spermatogenesis.