Morihana T, Kaneko A, Tomita F, Suwa T, Kohno Y, Kobayashi I
Department of Oral Surgery, Ashikaga Red Cross Hospital.
Jpn J Antibiot. 1989 Apr;42(4):973-82.
Clarithromycin (TE-031, A-56268), a new macrolide antibiotic, was administered to rats, and the distribution of the drug in the submandibular gland was studied using microautoradiography. The study revealed good accumulation of 14C-TE-031 in both the acini and the excretory ducts. TE-031 was administered to each of 3 healthy male volunteers in a single dose of 300 mg, and its concentrations in the serum and saliva was detected. Mean values of various pharmacokinetic parameters were as follows for the serum and saliva, respectively. Cmax 1.49 micrograms/ml and 1.93 micrograms/ml; Tmax 2.91 hours and 2.66 hours; T 1/2 6.31 hours and 4.15 hours; AUC 18.58 micrograms.hr/ml and 17.70 micrograms.hr/ml. Regarding the salivary bacterial flora, the total bacterial count decreased as the salivary TE-031 concentration increased, but it recovered to the initial level in 12 hours after administration. During the 24-hour period following an administration of TE-031, the salivary bacteria did not acquire resistance to the drug. Therefore, TE-031 is an antibiotic which exerts little effect on the normal salivary bacterial flora in short-term administration. Although the results differed among the individuals, the penetration of TE-031 to saliva was superior to that to the serum. Thus, TDM of TE-031 using salivary samples is possible.
新型大环内酯类抗生素克拉霉素（TE - 031，A - 56268）被给予大鼠，并使用微量放射自显影术研究了该药物在颌下腺中的分布。研究显示14C - TE - 031在腺泡和排泄管中均有良好的蓄积。给3名健康男性志愿者每人单次服用300mg TE - 031，并检测其血清和唾液中的浓度。血清和唾液的各种药代动力学参数平均值分别如下。Cmax为1.49微克/毫升和1.93微克/毫升；Tmax为2.91小时和2.66小时；T 1/2为6.31小时和4.15小时；AUC为18.58微克·小时/毫升和17.70微克·小时/毫升。关于唾液细菌菌群，随着唾液中TE - 031浓度的增加，细菌总数减少，但给药后12小时恢复到初始水平。在给予TE - 031后的24小时内，唾液细菌未对该药物产生耐药性。因此，TE - 031是一种在短期给药时对正常唾液细菌菌群影响较小的抗生素。尽管个体之间结果存在差异，但TE - 031在唾液中的渗透优于在血清中的渗透。因此，使用唾液样本进行TE - 031的治疗药物监测是可行的。
