Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.1.3.1 (alkaline phosphatase)
 47,916 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The clinical pharmacokinetics of teniposide (VM-26, NSC 122819) has been studied in 21 children (median age, 4.7 years) with acute lymphocytic leukemia. Teniposide was administered at a dosage of 165 mg/sq m as a 30- to 60-min i.v. infusion. Patients were studied either on the first or second dosage of the drug. Plasma samples were assayed for teniposide and metabolites by high-performance liquid chromatography with electro-chemical detection. Both compartmental and noncompartmental pharmacokinetic analyses were performed. Systemic clearance and apparent volume of distribution of steady state averaged 13.82 +/- 6.0 ml/min/sq m (S.D.) and 7.9 +/- 4.0 liter/sq m, respectively. Univariate and multivariate stepwise regression analyses were used to construct mathematical models to describe the relationships between certain patient-specific demographic and laboratory values and the pharmacokinetic parameters, systemic clearance, elimination rate constant, and area under the concentration-time curve. A significant relationship between serum alkaline phosphatase and systemic clearance, elimination rate constant, and area under the concentration-time curve was found, suggesting that liver function influences the disposition of this anticancer drug in humans.
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PMID:Teniposide (VM26) disposition in children with leukemia. 658 66

The pharmacodynamics of etoposide phosphate (Etopophos; Bristol-Myers Squibb Company, Princeton, NJ), a water-soluble prodrug of etoposide, was evaluated in 39 patients with solid tumors after a 30-minute intravenous infusion of escalating doses (equivalent to 50 to 175 mg/m2 of etoposide) on a day 1, 3, and 5 schedule of treatment. Serial blood samples were collected at predose and throughout the 32 hours following day 1 of treatment to determine the area under the plasma concentration-time curve (AUC) of etoposide phosphate and etoposide. Hematology profiles and serum chemistries were determined at predose and twice weekly for approximately 3 weeks after each treatment cycle. Both linear and nonlinear pharmacodynamic models were used to evaluate the relationship between hematologic toxicity and etoposide AUC and patient factors (age, gender, performance status, prior radiation therapy, prior chemotherapy, baseline albumin, bilirubin, alkaline phosphatase, creatinine, leukocyte count, granulocyte count). Etoposide phosphate was converted rapidly to etoposide in vivo. The ratio of the etoposide phosphate AUC to that of etoposide was < or = 1.2% indicating that etoposide was the main species in the systemic circulation. Myelosuppression was the dose-limiting toxicity, and significant decreases in white blood cell and granulocyte counts were noted. Hematologic toxicity was best described by a stepwise linear regression model consisting of etoposide AUC, serum albumin, and bilirubin. In summary, hematologic toxicity produced by the intravenous administration of etoposide phosphate correlates significantly with etoposide AUC and patient factors (baseline serum albumin and bilirubin) in cancer patients.
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PMID:A pharmacodynamic evaluation of hematologic toxicity observed with etoposide phosphate in the treatment of cancer patients. 899 71