Clinical phase I study of balofloxacin I. Single oral administration

• Published in: Japanese Journal of Chemotherapy Vol. 43; no. Supplement5; pp. 115 - 140
• Main Authors: Nakashima, Mitsuyoshi, Uematsu, Toshihiko, Fukuchi, Miho, Kosuge, Kazuhiro, Nakano, Mako
• Format: Journal Article
• Language: English; Japanese
• Published: Japanese Society of Chemotherapy 1995
• Subjects: Balofloxacin
• ISSN: 1340-7007; 1884-5886
• DOI: 10.11250/chemotherapy1995.43.Supplement5_115

Balofloxacin (BLFX) was orally administered to healthy male volunteers, and its safety and pharmacodynamics were investigated. A preliminary test was performed on two patients at each dose of 10mg, 20mg and 50mg during fasting by single administration. Subsequently, oral administration was initiated at 100mg, then gradually increased to 200 and 400 mg, as the test. The drug was administered at a dose of 200mg twice, before and after breakfast, to the same subject by the cross-over method in which a one-week drug-cessation period was included for the purpose of investigating the influence of meals. One patient in the group to which 200mg was administered postprandially had mild and transient dull headache, and one in the group to which 400mg was administered had symptoms resembling dizziness that disappeared about 10 minutes later. All the symptoms subsided rapidly without any specific treatment. No other problematic symptoms or findings were observed. The blood concentration increased in proportion to dose after the administration of BLFX. The maximum concentration (Cmax) was about 1μg/ml with the administration of 100mg, and about 2μg/ml with the administration of 200mg. The time of maximum concentration (Tmax) was 1.0-1.2 hours, and the half-life (T1/2) was 7.0-8.3 hours, showing rapid intestinal absorption and relatively long duration in the blood. Tmax was prolonged and Cmax was decreased by postprandial administration, but there seemed to be no influence on absorption, because the cumulative rate of urinary excretion was approximately equal to that with administration during fasting. Regardless of dose, the cumulative rate of urinary excretion was 70-80%. Glucuronic conjugated material was detected at about 4% and demethylated substance at about 0.4%. The rate of unchanged bodies recovered in the spontaneously excreted feces was 2.8-10.7%, showing a tendency for the urinary excretion rate to be low in the subjects who showed a high recovery rate. These results suggest that BLFX can be clinically administered in patients with infectious diseases, because it is safe and shows excellent pharmacodynamics.