Shiba K, Sakai O, Shimada J, Okazaki O, Aoki H, Hakusui H
Second Department of Internal Medicine, Jikei University School of Medicine, Tokyo, Japan.
Antimicrob Agents Chemother. 1992 Oct;36(10):2270-4. doi: 10.1128/AAC.36.10.2270.
This study examined the effects of widely used antacids (aluminum hydroxide, magnesium oxide, and calcium carbonate), ferrous sulfate, and ranitidine on the absorption of a fluorinated quinolone, (-)-(S)-9-fluoro-3-methyl-10-(4-methyl-1-piperazinyl)-7-oxo-2,3-dihydro- 7H- pyrido-[1,2,3,-de][1,4]benzoxazine-6-carboxylic acid hemihydrate (DR-3355), in healthy male volunteers enrolled in three separate randomized crossover studies. Study 1 used 100-mg doses of DR-3355 and concurrent doses of aluminum hydroxide (1 g) or magnesium oxide (500 mg), while study 2 used DR-3355 (100 mg) and concurrent ferrous sulfate (160 mg) or calcium carbonate (1 g). Study 3 used DR-3355 (100 mg) and concurrent ranitidine (150 mg). Each study included control doses of DR-3355 (100 mg) alone. When aluminum hydroxide, ferrous sulfate, and magnesium oxide were coadministered with DR-3355, the relative bioavailability of DR-3355 was decreased to 56, 81, and 78%, respectively, of that for DR-3355 (100 mg) alone. Urinary excretion of DR-3355 was also significantly decreased by coadministration of these drugs. Thus, the magnitude of the decrease in the area under the concentration-time curve for DR-3355 varied among antacids, and the ranking of their inhibitory effects correlated with previously reported rankings of stability constants for chelate formation. DR-3355 bioavailability was not influenced by the concurrent administration of calcium carbonate and ranitidine, indicating that changes in gastric pH do not affect DR-3355 absorption.
本研究在三项独立的随机交叉研究中，检测了广泛使用的抗酸剂（氢氧化铝、氧化镁和碳酸钙）、硫酸亚铁和雷尼替丁对一种氟喹诺酮类药物（-）-（S）-9-氟-3-甲基-10-（4-甲基-1-哌嗪基）-7-氧代-2,3-二氢-7H-吡啶并-[1,2,3,-de][1,4]苯并恶嗪-6-羧酸半水合物（DR-3355）在健康男性志愿者体内吸收的影响。研究1使用100mg剂量的DR-3355以及氢氧化铝（1g）或氧化镁（500mg）的同时给药剂量，而研究2使用DR-3355（100mg）以及硫酸亚铁（160mg）或碳酸钙（1g）的同时给药剂量。研究3使用DR-3355（100mg）以及雷尼替丁（150mg）的同时给药剂量。每项研究都包括单独使用DR-3355（100mg）的对照剂量。当氢氧化铝、硫酸亚铁和氧化镁与DR-3355合用时，DR-3355的相对生物利用度分别降至单独使用DR-3355（100mg）时的56%、81%和78%。这些药物的共同给药也显著降低了DR-3355的尿排泄量。因此，DR-3355浓度-时间曲线下面积的降低幅度在抗酸剂之间有所不同，其抑制作用的排名与先前报道的螯合物形成稳定性常数的排名相关。DR-3355的生物利用度不受碳酸钙和雷尼替丁同时给药的影响，这表明胃pH值的变化不会影响DR-3355的吸收。
