Maeda Miyuki, Nakano Yukitaka, Aoyama Takahiko, Matsumoto Yoshiaki, Fujito Hiroshi
Int J Clin Pharmacol Ther. 2016 Apr;54(4):263-8. doi: 10.5414/CP202423.
Azithromycin (AZM) is widely used as a first-line treatment option for children with mycoplasma pneumonia. Although pharmacists perform medication counseling in the pediatric ward, children often experience vomiting as a result of oral AZM administration. Drugs that are administered rectally are generally considered to enter the circulation system without passing through the liver first. The aim of our study was to prepare an AZM suppository and investigate the pharmaceutical properties and well as pharmacokinetics of the rectal administration route in humans.
Five healthy volunteers were enrolled in the study. All subjects provided written informed consent before participating in the study. Subjects were randomly assigned to either oral administration of oral AZM 500-mg tablet or rectal administration of 125-mg, 250-mg, or 500-mg AZM suppository. Blood samples for preparation of serum were collected predose as well as at 1, 2, 3, 4, 6, 12, and 24 hours following the first rectal dose. Serum concentrations of AZM were determined by high-performance liquid chromatography (HPLC) with electrochemical detection.
The bioavailability of the AZM suppository through rectal administration was 20.3% compared to oral administration. We hypothesize that the surface area where AZM is absorbed also affects the absorption by rectal administration. Although further investigation is necessary to improve the absorption of AZM by the rectum and to ensure safety in children, the AZM suppository may be an effective preparation in cases where oral administration is not tolerated.
阿奇霉素（AZM）被广泛用作支原体肺炎患儿的一线治疗选择。尽管药剂师在儿科病房进行用药咨询，但儿童口服AZM后常出现呕吐。直肠给药的药物通常被认为可不经肝脏首先进入循环系统。我们研究的目的是制备一种AZM栓剂，并研究其药学性质以及在人体直肠给药途径的药代动力学。
本研究纳入了5名健康志愿者。所有受试者在参与研究前均提供了书面知情同意书。受试者被随机分配为口服500mg的口服AZM片剂或直肠给予125mg、250mg或500mg的AZM栓剂。在首次直肠给药前以及给药后1、2、3、4、6、12和24小时采集用于制备血清的血样。通过高效液相色谱（HPLC）和电化学检测法测定血清中AZM的浓度。
与口服给药相比，AZM栓剂直肠给药的生物利用度为20.3%。我们推测AZM吸收的表面积也会影响直肠给药的吸收。尽管需要进一步研究以提高AZM经直肠的吸收并确保儿童用药安全，但在无法耐受口服给药的情况下，AZM栓剂可能是一种有效的制剂。
