TY - JOUR
T1 - Pharmacokinetics (PK) of micronized carboxyamido-triazole(CAI) in cancer patients (PTS)
AU - Bauer, K. S.
AU - Kohn, E. C.
AU - Reed, E.
AU - Sarosy, G. A.
AU - Lush, R. M.
AU - Simmons, B. R.
AU - Davis, P. A.
AU - Figg, W. D.
PY - 1997
Y1 - 1997
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=33748965403&partnerID=8YFLogxK
M3 - Article
AN - SCOPUS:33748965403
SN - 0009-9236
VL - 61
SP - 146
JO - Clinical Pharmacology and Therapeutics
JF - Clinical Pharmacology and Therapeutics
IS - 2
ER -