Pharmacokinetics (PK) of micronized carboxyamido-triazole(CAI) in cancer patients (PTS)

K. S. Bauer*, E. C. Kohn, E. Reed, G. A. Sarosy, R. M. Lush, B. R. Simmons, P. A. Davis, W. D. Figg

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

CAI, a synthetic inhibitor of non-voltage-induced calcium mediated signal transduction, has demonstrated antiproliferative, antimetastatic, and antiangiogenic properties. Single dose micronized encapsulated CAI (100-350 mg/m2/d) was administered to 18 pts with refractory solid tumors, as well, 18 pts received daily dosing for 8 to >270 days, PK parameters were obtained by weighted nonlinear least squares analysis using ADAPT IIv4. Bayesian priors for determination of multiple dosing parameters were obtained from the test dose. These parameters were obtained by MAP Bayesian probability, fitting a one compartment open-linear model. Single Dose (SD) Multiple Dose (MD) Cl/F (L/h) 17.5 ± 28.1 8.73 ± 9.53 Vd/F (L) 371.3 ± 552.8 247.0 ± 160.5 t1/2 (h) 33.8 ± 23.4 60.0 ± 93.7 Mean ± standard deviation The PK of CAI were best described by a one compartment open linear model and parameters did not differ significantly between single and multiple doses, with the exception of ka which was greater in the SD data. Neurotoxicity was the DLT, a pharmacodynamic analysis of toxicity has also been performed.

Original languageEnglish
Pages (from-to)146
Number of pages1
JournalClinical Pharmacology and Therapeutics
Volume61
Issue number2
StatePublished - 1997
Externally publishedYes

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