Gan V N, McCarty J M, Chu S Y, Carr R
Children's Medical Center of Dallas, TX 75235, USA.
Pediatr Infect Dis J. 1997 Jan;16(1):39-43. doi: 10.1097/00006454-199701000-00009.
To determine the steady state plasma and middle ear fluid concentrations of clarithromycin and its metabolite, 14(R)-hydroxyclarithromycin in 32 pediatric patients with acute otitis media.
After the sixth dose of a 7.5-mg/kg every-12-h regimen of clarithromycin suspension, tympanocentesis was performed at 2, 4, 8 or 12 hours postdose. Plasma and middle ear fluid samples were assayed for concentrations of clarithromycin and its 14-hydroxy metabolite.
Mean middle ear fluid concentrations ranged from 3.0 to 8.3 micrograms/g during the dosing interval for clarithromycin and from 1.5 to 3.8 micrograms/g for 14(R)-hydroxyclarithromycin. The mean middle ear fluid concentrations were consistently greater than corresponding mean plasma concentrations, which ranged from 0.7 to 3.4 micrograms/ml for clarithromycin and from 0.8 to 1.8 micrograms/ml for 14(R)-hydroxyclarithromycin. The ratios of middle ear fluid to plasma concentration appeared to increase during the dosing interval and were 8.8 and 3.8 for clarithromycin and 14(R)-hydroxyclarithromycin, respectively, 12 h after dosing.
Multiple oral doses of clarithromycin suspension produced sustained middle ear fluid concentrations of clarithromycin and 14(R)-hydroxyclarithromycin which exceed the minimum inhibitory concentrations of most otic pathogens.
测定32例急性中耳炎患儿中克拉霉素及其代谢产物14（R）-羟基克拉霉素的稳态血浆和中耳液浓度。
在给予每12小时一次、每次7.5mg/kg的克拉霉素悬浮液第六剂后，于给药后2、4、8或12小时进行鼓膜穿刺术。测定血浆和中耳液样本中克拉霉素及其14-羟基代谢产物的浓度。
在给药间隔期间，克拉霉素的中耳液平均浓度范围为3.0至8.3微克/克，14（R）-羟基克拉霉素为1.5至3.8微克/克。中耳液平均浓度始终高于相应的血浆平均浓度，克拉霉素的血浆平均浓度范围为0.7至3.4微克/毫升，14（R）-羟基克拉霉素为0.8至1.8微克/毫升。给药间隔期间，中耳液与血浆浓度之比似乎增加，给药12小时后，克拉霉素和14（R）-羟基克拉霉素的该比值分别为8.8和3.8。
多次口服克拉霉素悬浮液可使中耳液中克拉霉素和14（R）-羟基克拉霉素的浓度持续升高，超过大多数耳部病原体的最低抑菌浓度。
