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Pharmacokinetics and Safety of CXA-101, a New Antipseudomonal Cephalosporin, in Healthy Adult Male and Female Subjects Receiving Single- and Multiple-Dose Intravenous Infusions
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| Zeitschriftentitel: | Antimicrobial Agents and Chemotherapy |
|---|---|
| Personen und Körperschaften: | , , , |
| In: | Antimicrobial Agents and Chemotherapy, 54, 2010, 8, S. 3427-3431 |
| Format: | E-Article |
| Sprache: | Englisch |
| veröffentlicht: |
American Society for Microbiology
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| Schlagwörter: |
| author_facet |
Ge, Yigong Whitehouse, M. J. Friedland, Ian Talbot, George H. Ge, Yigong Whitehouse, M. J. Friedland, Ian Talbot, George H. |
|---|---|
| author |
Ge, Yigong Whitehouse, M. J. Friedland, Ian Talbot, George H. |
| spellingShingle |
Ge, Yigong Whitehouse, M. J. Friedland, Ian Talbot, George H. Antimicrobial Agents and Chemotherapy Pharmacokinetics and Safety of CXA-101, a New Antipseudomonal Cephalosporin, in Healthy Adult Male and Female Subjects Receiving Single- and Multiple-Dose Intravenous Infusions Infectious Diseases Pharmacology (medical) Pharmacology |
| author_sort |
ge, yigong |
| spelling |
Ge, Yigong Whitehouse, M. J. Friedland, Ian Talbot, George H. 0066-4804 1098-6596 American Society for Microbiology Infectious Diseases Pharmacology (medical) Pharmacology http://dx.doi.org/10.1128/aac.01753-09 <jats:title>ABSTRACT</jats:title> <jats:p>CXA-101 is a novel, broad-spectrum cephalosporin with excellent antipseudomonal activity. A Phase 1 study was performed to determine the safety, tolerability, and pharmacokinetics of CXA-101 after single- and multiple-dose intravenous administration over 1 h to healthy male and female subjects. In part 1 of the study, five cohorts of eight subjects each (six receiving CXA-101 and two receiving a placebo) received single ascending doses of 250, 500, 1,000, 1,500, and 2,000 mg. In part 2, cohorts 1 and 2 received 500 mg and 1,000 mg, respectively, every 8 h, and cohort 3 received 1,500 mg every 12 h; each cohort received dosing for 10 days. Standard safety and tolerability assessments were performed. Blood and urine pharmacokinetic samples were assayed by a validated bioanalytical method and analyzed using standard noncompartmental methodology. All 64 subjects completed dosing; none withdrew from the study. Drug-related systemic adverse events were infrequent and mild. Mild, non-treatment-limiting infusion site events occurred during multiple-dose administration. No clinically significant laboratory or electrocardiographic finding or dose-limiting toxicity was observed. CXA-101 exhibited dose-linear pharmacokinetics; the mean plasma half-life was ∼2.3 h. More than 90% of the administered dose was eliminated unchanged through renal excretion. In summary, CXA-101 administered as a 1-hour infusion was generally safe and well tolerated in single doses up to 2,000 mg and in multiple doses up to 3 g daily over 10 days. The favorable safety and predictable pharmacokinetic profile of CXA-101 support its continuing clinical development for the treatment of serious bacterial infections.</jats:p> Pharmacokinetics and Safety of CXA-101, a New Antipseudomonal Cephalosporin, in Healthy Adult Male and Female Subjects Receiving Single- and Multiple-Dose Intravenous Infusions Antimicrobial Agents and Chemotherapy |
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| title |
Pharmacokinetics and Safety of CXA-101, a New Antipseudomonal Cephalosporin, in Healthy Adult Male and Female Subjects Receiving Single- and Multiple-Dose Intravenous Infusions |
| title_unstemmed |
Pharmacokinetics and Safety of CXA-101, a New Antipseudomonal Cephalosporin, in Healthy Adult Male and Female Subjects Receiving Single- and Multiple-Dose Intravenous Infusions |
| title_full |
Pharmacokinetics and Safety of CXA-101, a New Antipseudomonal Cephalosporin, in Healthy Adult Male and Female Subjects Receiving Single- and Multiple-Dose Intravenous Infusions |
| title_fullStr |
Pharmacokinetics and Safety of CXA-101, a New Antipseudomonal Cephalosporin, in Healthy Adult Male and Female Subjects Receiving Single- and Multiple-Dose Intravenous Infusions |
| title_full_unstemmed |
Pharmacokinetics and Safety of CXA-101, a New Antipseudomonal Cephalosporin, in Healthy Adult Male and Female Subjects Receiving Single- and Multiple-Dose Intravenous Infusions |
| title_short |
Pharmacokinetics and Safety of CXA-101, a New Antipseudomonal Cephalosporin, in Healthy Adult Male and Female Subjects Receiving Single- and Multiple-Dose Intravenous Infusions |
| title_sort |
pharmacokinetics and safety of cxa-101, a new antipseudomonal cephalosporin, in healthy adult male and female subjects receiving single- and multiple-dose intravenous infusions |
| topic |
Infectious Diseases Pharmacology (medical) Pharmacology |
| url |
http://dx.doi.org/10.1128/aac.01753-09 |
| publishDate |
2010 |
| physical |
3427-3431 |
| description |
<jats:title>ABSTRACT</jats:title>
<jats:p>CXA-101 is a novel, broad-spectrum cephalosporin with excellent antipseudomonal activity. A Phase 1 study was performed to determine the safety, tolerability, and pharmacokinetics of CXA-101 after single- and multiple-dose intravenous administration over 1 h to healthy male and female subjects. In part 1 of the study, five cohorts of eight subjects each (six receiving CXA-101 and two receiving a placebo) received single ascending doses of 250, 500, 1,000, 1,500, and 2,000 mg. In part 2, cohorts 1 and 2 received 500 mg and 1,000 mg, respectively, every 8 h, and cohort 3 received 1,500 mg every 12 h; each cohort received dosing for 10 days. Standard safety and tolerability assessments were performed. Blood and urine pharmacokinetic samples were assayed by a validated bioanalytical method and analyzed using standard noncompartmental methodology. All 64 subjects completed dosing; none withdrew from the study. Drug-related systemic adverse events were infrequent and mild. Mild, non-treatment-limiting infusion site events occurred during multiple-dose administration. No clinically significant laboratory or electrocardiographic finding or dose-limiting toxicity was observed. CXA-101 exhibited dose-linear pharmacokinetics; the mean plasma half-life was ∼2.3 h. More than 90% of the administered dose was eliminated unchanged through renal excretion. In summary, CXA-101 administered as a 1-hour infusion was generally safe and well tolerated in single doses up to 2,000 mg and in multiple doses up to 3 g daily over 10 days. The favorable safety and predictable pharmacokinetic profile of CXA-101 support its continuing clinical development for the treatment of serious bacterial infections.</jats:p> |
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| description | <jats:title>ABSTRACT</jats:title> <jats:p>CXA-101 is a novel, broad-spectrum cephalosporin with excellent antipseudomonal activity. A Phase 1 study was performed to determine the safety, tolerability, and pharmacokinetics of CXA-101 after single- and multiple-dose intravenous administration over 1 h to healthy male and female subjects. In part 1 of the study, five cohorts of eight subjects each (six receiving CXA-101 and two receiving a placebo) received single ascending doses of 250, 500, 1,000, 1,500, and 2,000 mg. In part 2, cohorts 1 and 2 received 500 mg and 1,000 mg, respectively, every 8 h, and cohort 3 received 1,500 mg every 12 h; each cohort received dosing for 10 days. Standard safety and tolerability assessments were performed. Blood and urine pharmacokinetic samples were assayed by a validated bioanalytical method and analyzed using standard noncompartmental methodology. All 64 subjects completed dosing; none withdrew from the study. Drug-related systemic adverse events were infrequent and mild. Mild, non-treatment-limiting infusion site events occurred during multiple-dose administration. No clinically significant laboratory or electrocardiographic finding or dose-limiting toxicity was observed. CXA-101 exhibited dose-linear pharmacokinetics; the mean plasma half-life was ∼2.3 h. More than 90% of the administered dose was eliminated unchanged through renal excretion. In summary, CXA-101 administered as a 1-hour infusion was generally safe and well tolerated in single doses up to 2,000 mg and in multiple doses up to 3 g daily over 10 days. The favorable safety and predictable pharmacokinetic profile of CXA-101 support its continuing clinical development for the treatment of serious bacterial infections.</jats:p> |
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| spelling | Ge, Yigong Whitehouse, M. J. Friedland, Ian Talbot, George H. 0066-4804 1098-6596 American Society for Microbiology Infectious Diseases Pharmacology (medical) Pharmacology http://dx.doi.org/10.1128/aac.01753-09 <jats:title>ABSTRACT</jats:title> <jats:p>CXA-101 is a novel, broad-spectrum cephalosporin with excellent antipseudomonal activity. A Phase 1 study was performed to determine the safety, tolerability, and pharmacokinetics of CXA-101 after single- and multiple-dose intravenous administration over 1 h to healthy male and female subjects. In part 1 of the study, five cohorts of eight subjects each (six receiving CXA-101 and two receiving a placebo) received single ascending doses of 250, 500, 1,000, 1,500, and 2,000 mg. In part 2, cohorts 1 and 2 received 500 mg and 1,000 mg, respectively, every 8 h, and cohort 3 received 1,500 mg every 12 h; each cohort received dosing for 10 days. Standard safety and tolerability assessments were performed. Blood and urine pharmacokinetic samples were assayed by a validated bioanalytical method and analyzed using standard noncompartmental methodology. All 64 subjects completed dosing; none withdrew from the study. Drug-related systemic adverse events were infrequent and mild. Mild, non-treatment-limiting infusion site events occurred during multiple-dose administration. No clinically significant laboratory or electrocardiographic finding or dose-limiting toxicity was observed. CXA-101 exhibited dose-linear pharmacokinetics; the mean plasma half-life was ∼2.3 h. More than 90% of the administered dose was eliminated unchanged through renal excretion. In summary, CXA-101 administered as a 1-hour infusion was generally safe and well tolerated in single doses up to 2,000 mg and in multiple doses up to 3 g daily over 10 days. The favorable safety and predictable pharmacokinetic profile of CXA-101 support its continuing clinical development for the treatment of serious bacterial infections.</jats:p> Pharmacokinetics and Safety of CXA-101, a New Antipseudomonal Cephalosporin, in Healthy Adult Male and Female Subjects Receiving Single- and Multiple-Dose Intravenous Infusions Antimicrobial Agents and Chemotherapy |
| spellingShingle | Ge, Yigong, Whitehouse, M. J., Friedland, Ian, Talbot, George H., Antimicrobial Agents and Chemotherapy, Pharmacokinetics and Safety of CXA-101, a New Antipseudomonal Cephalosporin, in Healthy Adult Male and Female Subjects Receiving Single- and Multiple-Dose Intravenous Infusions, Infectious Diseases, Pharmacology (medical), Pharmacology |
| title | Pharmacokinetics and Safety of CXA-101, a New Antipseudomonal Cephalosporin, in Healthy Adult Male and Female Subjects Receiving Single- and Multiple-Dose Intravenous Infusions |
| title_full | Pharmacokinetics and Safety of CXA-101, a New Antipseudomonal Cephalosporin, in Healthy Adult Male and Female Subjects Receiving Single- and Multiple-Dose Intravenous Infusions |
| title_fullStr | Pharmacokinetics and Safety of CXA-101, a New Antipseudomonal Cephalosporin, in Healthy Adult Male and Female Subjects Receiving Single- and Multiple-Dose Intravenous Infusions |
| title_full_unstemmed | Pharmacokinetics and Safety of CXA-101, a New Antipseudomonal Cephalosporin, in Healthy Adult Male and Female Subjects Receiving Single- and Multiple-Dose Intravenous Infusions |
| title_short | Pharmacokinetics and Safety of CXA-101, a New Antipseudomonal Cephalosporin, in Healthy Adult Male and Female Subjects Receiving Single- and Multiple-Dose Intravenous Infusions |
| title_sort | pharmacokinetics and safety of cxa-101, a new antipseudomonal cephalosporin, in healthy adult male and female subjects receiving single- and multiple-dose intravenous infusions |
| title_unstemmed | Pharmacokinetics and Safety of CXA-101, a New Antipseudomonal Cephalosporin, in Healthy Adult Male and Female Subjects Receiving Single- and Multiple-Dose Intravenous Infusions |
| topic | Infectious Diseases, Pharmacology (medical), Pharmacology |
| url | http://dx.doi.org/10.1128/aac.01753-09 |