Manual and automatic extraction and high-performance liquid chromatographic determination of a spicamycin derivative, KRN5500, in rat plasma

Yoshioka, Eiji; Morino, Michiyo; Tanaka, Hideji; Shinkai, Hiroshi

doi:10.1016/s0378-4347(96)00430-6

Cited by 2 publications

(1 citation statement)

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“…KRN5500 assay. KRN5500 in plasma and urine samples was measured using a modified reverse phase HPLC method with Spicamycin-65 (SPK-65) as internal standard following solid phase extraction [15]. To 1 ml plasma, 2 ml of chilled methanol was added and vortexed for 10 s. The sample was kept on ice for 5 min and then centrifuged for 5 min.…”

Section: Pharmacokinetic and Pharmacodynamic Studiesmentioning

confidence: 99%

A Phase I Clinical Trial of Spicamycin Derivative KRN5500 (NSC 650426) Using a Phase I Accelerated Titration “2B” Design

et al. 2003

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The spicamycin derivative KRN5500 was considered as a potential anti-cancer agent based on in vitro and preclinical studies. A Phase I study involving 24 cancer patients in whom tumors were refractory to all other conventional therapies was conducted to determine the dose limiting toxicity, maximum tolerated dose, effectiveness, and pharmacokinetic parameters of this drug administered by 1-h IV infusion daily for five consecutive days every 3 weeks. Using an accelerated dose titration strategy, 8.4 mg/m2/d x 5 days was the maximum administered dose. Severe gastrointestinal and hepatic toxicities were observed at doses at or above 4.3 mg/m2/d x 5. The recommended Phase II dose i s 4.3mg/m2/d x 5. The distribution of KRN5500 followed a two-compartment model, and clearance did not decrease significantly over the dose range 0.8-8.4 mg/m2/d x 5. No significant correlation was observed between plasma levels and toxicity. No tumor responses were observed among the 14 patients evaluable for response.

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Section: Pharmacokinetic and Pharmacodynamic Studiesmentioning

confidence: 99%