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Miles, Dale R.; Smith, Jennifer A.; Phan, See-Chun; Hutcheson, Sammy J.; Renschler, Markus F.; Ford, Judith M.; Boswell, Garry W.
Journal of clinical pharmacology, 03/2005, Letnik: 45, Številka: 3Journal Article
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 (V1) was 21% lower in women and increased with increasing serum creatinine. For all covariates, except sex and phenytoin, the predicted change in CL or V1 (5th and 95th percentiles) varied ≤13% from the population mean CL or V1 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.
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Leto | Faktor vpliva | Izdaja | Kategorija | Razvrstitev | ||||
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JCR | SNIP | JCR | SNIP | JCR | SNIP | JCR | SNIP |
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