Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0012833 (dizziness)
 9,689 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Trospectomycin sulfate is a novel aminocyclitol antibiotic. This study evaluated the tolerance and the pharmacokinetics of multiple, intravenous doses of trospectomycin (TRO) in healthy male volunteers. Three groups of 10 volunteers were studied. Eight volunteers in each group were studied in a parallel design to receive trospectomycin (Group 1 = 250 mg, Group 2 = 500 mg, Group 3 = 750 mg) while 2 volunteers received placebo (normal saline). Drug doses were administered in 30 ml volumes over 30 min every 8 h for 7 days (i.e. 21 total doses). Evaluations of vital signs, side effects, and safety laboratory tests were made at regular intervals during the study. The most frequent medical events observed in the volunteers receiving trospectomycin were perioral/facial paresthesias (54%), pain at the i.v. infusion site (46%), dizziness/lightheadedness (58%), and GI symptoms (38%). A statistically significant dose response relationship was observed for the incidence of perioral/facial paresthesias and pain at the i.v. infusion site (i.e., increased incidence with increased dose). All the medical events were mild or moderate in severity and reversible following drug discontinuation. In the 500 and 750 mg trospectomycin groups, standing systolic blood pressure decreased significantly with the first dose of study drug. Elevated levels of SGPT were observed in 9 volunteers (1 in placebo, 3 in 250 mg, 1 in 500 mg, and 4 in 750 mg dose groups). This study demonstrates that multiple intravenous trospectomycin doses up to 750 mg are reasonably well tolerated in healthy male volunteers. The concentration of trospectomycin in serum, measured with a sensitive HPLC assay, was less than 3 mcg/ml at 8 h postinfusion for all dose levels.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Multiple-dose, double-blind, placebo controlled intravenous tolerance and pharmacokinetic study of trospectomycin sulfate (U-63, 366F) in healthy male volunteers. 214 31

In this study, local and systemic tolerance and pharmacokinetics of trospectomycin sulfate in human beings were evaluated for the first time. Trospectomycin sulfate (U-63,366F; trospectomycin) or sterile saline was administered to 96 healthy male volunteers in doses ranging from 0.25 ml (75 mg) to 3.3 ml (1,000 mg) in a single intramuscular injection in a double-blind, randomized design. Volunteers were screened to establish baseline vital signs and laboratory test values. Pain and tenderness at the injection site, which occurred at doses of 450 mg and above, were the most common side effects; they were mild in severity and transient. Adverse drug experiences reported by subjects included nausea, dizziness, light-headedness, diaphoresis, costal pain, and perioral numbness. The perioral numbness (paresthesia) experienced at doses of 750, 900, and 1,000 mg was probably drug related. No Clostridium difficile toxin was detected in fecal samples. Pharmacokinetic calculations based on data obtained by high-performance liquid chromatography showed that after a 1,000-mg intramuscular dose of trospectomycin (3.3 ml), the serum mean half-life was 1.85 h (1.70 to 2.02 h), mean area under the serum concentration-time curve was 140.2 micrograms.h/ml and was linear with dose, mean peak concentration was 28.3 micrograms/ml (20.4 to 34.7 micrograms/ml), mean time to maximum concentration was 71 min (30 to 120 min), and the elimination rate constant was 0.307 h-1. The elimination rate constant and half-life did not vary with dose. Little trospectomycin was detected in 2-day fecal collections. A few randomly occurring abnormal clinical laboratory test values and vital signs were observed. For the trospectomycin-treated group, creatinine phosphokinase increased substantially for 24 h after injection and then decrease through day 5, while serum glutamic oxalacetic transaminase and lactate dehydrogenase increased slightly.
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PMID:Human safety and pharmacokinetics of a single intramuscular dose of a novel spectinomycin analog, trospectomycin (U-63,366F). 215 Sep 7