Reversed-phase liquid chromatography of biologically active lipophilic chelators

Ioffe, V; Kalendarev, T; Rubinstein, Irina; Mizerikhin, E; Tsibulsky, E

doi:10.1016/s0021-9673(02)01450-4

Cited by 2 publications

(1 citation statement)

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“…Reversed-phase liquid chromatography methods have been previously reported for the separation of the long-chain aliphatic esters of BAPTA and their impurities [8,9]. In our previous paper, a LC-MS/MS method was developed for the determination of BAPTA-AM in rat plasma [6].…”

Section: Introductionmentioning

confidence: 99%

Determination of 1,2-bis (2-aminophenoxy)ethane-N,N,N′,N′-tetraacetic acid (BAPTA free acid) in rat plasma, urine and feces by liquid chromatography with UV and tandem mass spectrometric detection

Zheng

Liu

2010

Journal of Chromatography B

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Section: Introductionmentioning

confidence: 99%

Determination of 1,2-bis (2-aminophenoxy)ethane-N,N,N′,N′-tetraacetic acid (BAPTA free acid) in rat plasma, urine and feces by liquid chromatography with UV and tandem mass spectrometric detection

Zheng

Liu

2010

Journal of Chromatography B

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Clinical pharmacology of DP‐b99 in healthy volunteers: First administration to humans

Rosenberg¹,

Angel²,

Kozak³

2005

Brit J Clinical Pharma

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AimsTo investigate the safety, tolerability and pharmacokinetics of DP-b99 in healthy volunteers. DP-b99 is a newly developed lipophilic, cell permeable derivative of BAPTA (1,2-bis(2-aminophenoxy)ethane-N,N,N ¢ ,N ¢ -tetraacetic acid), which selectively modulates the distribution of metal ions in hydrophobic milieu, and is in clinical development as a neuroprotectant for cerebral ischaemic stroke. To our knowledge no BAPTA derivative has ever been administered to man. Here we repor t the first human administration of DP-b99 in a phase I, two-part, double-blind, randomized placebo controlled study, with single IV doses of 0.003-1.0 mg kg -1 day -1 DP-b99 (part 1) or multiple ascending doses of 0.03-1.0 mg kg -1 day -1 DP-b99 over 4 days (part 2). MethodsA double-blind, dose escalating tolerability study of DP-b99 in normal (young -aged between 18 and 40 years and elderly -aged between 65 and 85 years) healthy adult male volunteers was conducted. Part 1 of the study investigated single administration of ascending intravenous doses, and part 2 examined the effects of ascending doses given repeatedly over 4 days . Twenty-four young volunteers in part 1 received single dose administrations and 26 young volunteers in part 2 received repeated ascending dose administrations of either intravenous DP-b99 or placebo. Subsequently, 10 elderly volunteers received repeated intravenous DP-b99 (1 mg kg -1 ) or placebo in part 2 over 4 days. Adverse events were identified by either subject self reporting or based upon laboratory parameters (blood chemistry, complete blood cell count, prothrombin time (PT), activated partial thromboplastin (PTT), physical examination, vital signs (blood pressure, pulse rate, respiratory rate, body temperature) and urinalysis. A comprehensive set of cardiovascular parameters was assessed as well (blood pressure, 12 lead-ECG recordings and continuous bedside cardiac monitoring for 6 h on day 1). ResultsThe administration of DP-b99 up to the highest dose of 1.0 mg kg -1 was well tolerated and had an acceptable safety profile up to the highest dose of 1.0 mg kg -1 tested in both study parts. No serious or severe adverse events were encountered. Eight mild to moderate adverse events were observed in six of the seven young subjects treated with four repeated doses of 1.0 mg kg -1 , with reversible phlebitis being the most frequently reported adverse event. The drug was tolerated better at the injection site by the elderly group compared with the younger subjects. No adverse effects were observed in cardiovascular parameters sensitive to trans-membranous calcium concentrations. The pharmacokinetic parameters were derived by noncompar tmental analysis. On day 1 following administration of 1 mg kg -1 the mean half-life of DP-b99 in young volunteers was 3.47 ± 0.90 h and in the elderly was 2.11 ± 0.09 h. On day 4 following the same administration of DP-b99 the mean half-life was 4.36 ± 1.49 and 2.10 ± 1.14 h in the young and elderly, respectively. There was higher systemic G. Rosenberg et al. 860 :1 Br J ...

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Reversed-phase liquid chromatography of biologically active lipophilic chelators

Cited by 2 publications

References 1 publication

Determination of 1,2-bis (2-aminophenoxy)ethane-N,N,N′,N′-tetraacetic acid (BAPTA free acid) in rat plasma, urine and feces by liquid chromatography with UV and tandem mass spectrometric detection

Determination of 1,2-bis (2-aminophenoxy)ethane-N,N,N′,N′-tetraacetic acid (BAPTA free acid) in rat plasma, urine and feces by liquid chromatography with UV and tandem mass spectrometric detection

Clinical pharmacology of DP‐b99 in healthy volunteers: First administration to humans

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