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Population Pharmacokinetics of Motexafin Gadolinium in Adults With Brain Metastases or Glioblastoma Multiforme
Author(s) -
Miles Dale R.,
Smith Jennifer A.,
Phan SeeChun,
Hutcheson Sammy J.,
Renschler Markus F.,
Ford Judith M.,
Boswell Garry W.
Publication year - 2005
Publication title -
the journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.92
H-Index - 116
eISSN - 1552-4604
pISSN - 0091-2700
DOI - 10.1177/0091270004271946
Subject(s) - pharmacokinetics , medicine , population , creatinine , urology , hemoglobin , renal function , alkaline phosphatase , pharmacology , chemistry , biochemistry , environmental health , enzyme
The purpose of this study was to determine clinical variables affecting motexafin gadolinium (MGd) pharmacokinetics. Motexafin gadolinium (4–5.3 mg/kg/d) was administered intravenously for 2 to 6.5 weeks. Plasma samples from 3 clinical trials were analyzed for MGd using liquid chromatography/mass spectroscopy. The pooled data were analyzed using population pharmacokinetic (POP‐PK) methods. The POP‐PK model included 243 patients (1575 samples). Clearance (CL) was 14% lower in women, but weight‐normalized clearance was only 5% lower in women. Clearance decreased with increasing alkaline phosphatase, increasing age, and decreasing hemoglobin. Administration of phenytoin increased CL by approximately 30%. Central compartment volume (V 1 ) was 21% lower in women and increased with increasing serum creatinine. For all covariates, except sex and phenytoin, the predicted change in CL or V 1 (5th and 95th percentiles) varied ≤13% from the population mean CL or V 1 estimate. It was concluded that a 3‐compartment, open, POP‐PK model predicts small but significant effects of age, sex, alkaline phosphatase, hemoglobin, serum creatinine, and phenytoin on MGd pharmacokinetics.