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Biomedical subjects

David J Freeman

Publications and source records attributed to David J Freeman.

5 recordsLinked to original sources
PubMed2003

Monitoring clozapine: are fingerprick blood and plasma clozapine levels equivalent to arm venipuncture blood and plasma levels?

The objective of this pilot study was to determine whether fingerprick blood and plasma clozapine levels were equivalent to arm venipuncture blood and plasma levels for the purpose of therapeutic monitoring. A convenient sample of 10 outpatients from the Elgin Program of Assertive Community Treatment Team (PACT) participated in the study. Blood samples were obtained simultaneously from both the arm and finger in patients at steady state to measure clozapine levels. Each site provided a blood and plasma clozapine level, and they were compared. Clozapine levels from arm and finger sites were found to be equivalent in both blood and plasma. Although plasma clozapine levels were consistently greater than those in whole blood by a mean value of 27%, the plasma therapeutic threshold level (350-400 micro g/L) was considered an adequate target for monitoring. A fingerprick blood sample of 50 micro L was sufficient to measure clozapine levels accurately at steady state. We therefore concluded that fingerprick blood testing is as effective as the traditional arm venipuncture method in obtaining accurate clozapine levels. This procedure may provide certain benefits for the seriously mentally ill.

Adult↗
PubMed2003

Relative bioavailability and antioxidant potential of two coenzyme q10 preparations.

Coenzyme Q10 (CoQ10) is synthesized by the human body and found in certain foods. Daily supplementation of CoQ10 could protect against heart disease but the bioavailability of CoQ10 supplements depends on the formulation taken. We compared the bioavailability and antioxidant properties of two commercial CoQ10 formulations, a commercial grade CoQ10 powder (commercial grade CoQ) and a new BT-CoQ10 BIO-TRANSFORMED (BT-CoQ10) obtained by fermentation of a soy-based, CoQ10-rich media with baker's yeast. Eleven healthy individuals participated in a randomized two-way crossover trial, with a 3-week washout period. Capsules containing 300 mg of either BT-CoQ10 or commercial grade CoQ10 were given daily for 1 week and multiple blood samples were taken for CoQ10, glutathione and glutathione peroxidase (GPx) determination. In 3 subjects, baseline plasma CoQ10 levels were lower prior to BT than prior to commercial grade CoQ treatment. In the remaining participants, ingestion of BT vs. commercial grade CoQ significantly increased maximum plasma CoQ10 concentration (+126%, p = 0.04) and tended to increase CoQ10 area under the curve from 0 to 24 h (+160%, p = 0.07). One week of treatment with each formulation increased plasma CoQ10 but did not alter plasma glutathione or GPx activity. The enhanced bioavailability of the BT product might be due to its predominantly reduced, hydrophilic membrane-complex form.

Adult↗
PubMed2002

Fruit juices inhibit organic anion transporting polypeptide-mediated drug uptake to decrease the oral availability of fexofenadine.

OBJECTIVES: Our objective was to examine the effect of different fruits and their constituents on P-glycoprotein and organic anion transporting polypeptide (OATP) activities in vitro and on drug disposition in humans. METHODS: P-glycoprotein-mediated digoxin or vinblastine efflux was determined in polarized epithelial cell monolayers. OATP-mediated fexofenadine uptake was measured in a transfected cell line. The oral pharmacokinetics of 120 mg fexofenadine was assessed with water, 25%-strength grapefruit juice, or normal-strength grapefruit, orange, or apple juices (1.2 L over 3 hours) in a randomized 5-way crossover study in 10 healthy subjects. RESULTS: Grapefruit juice and segments and apple juice at 5% of normal strength did not alter P-glycoprotein activity. Grapefruit extract reduced transport. 6',7'-Dihydroxybergamottin had modest inhibitory activity (50% inhibitory concentration [IC(50)], 33 micromol/L). In contrast, grapefruit, orange, and apple juices at 5% of normal strength markedly reduced human OATP and rat oatp activity. 6',7'-Dihydroxybergamottin potently inhibited rat oatp3 and oatp1 (IC(50), 0.28 micromol/L). Other furanocoumarins and bioflavonoids also reduced rat oatp3 activity. Grapefruit, orange, and apple juices decreased the fexofenadine area under the plasma concentration-time curve (AUC), the peak plasma drug concentration (C(max)), and the urinary excretion values to 30% to 40% of those with water, with no change in the time to reach C(max), elimination half-life, renal clearance, or urine volume in humans. Change in fexofenadine AUC with juice was variable among individuals and inversely dependent on value with water. CONCLUSIONS: Fruit juices and constituents are more potent inhibitors of OATPs than P-glycoprotein activities, which can reduce oral drug bioavailability. Results support a new model of intestinal drug absorption and mechanism of food-drug interaction.

ATP Binding Cassette Transporter, Subfamily B↗
PubMed2002

Relation of blood counts during clozapine treatment to serum concentrations of clozapine and nor-clozapine.

OBJECTIVE: To determine the relation between serum clozapine and nor-clozapine levels and blood cell counts during clozapine treatment. METHOD: We undertook a prospective longitudinal study of 37 consecutive patients with a diagnosis of schizophrenia treated with clozapine. We obtained informed consent and then determined serum concentrations of clozapine and nor-clozapine weekly. Clozapine was administered daily in divided doses given every 12 hours and adjusted according to clinical guidelines for its use. Samples for serum concentrations were taken at steady state, immediately before the next morning's dose, for 4 to 8 weeks. Complete blood counts (CBC), weight, and vital signs (that is, blood pressure, pulse, and temperature) were also monitored weekly before the morning's dose of clozapine was administered. RESULTS: Analyses of variance showed no significant changes over the 8-week treatment course in the observed mean white blood count (WBC), red blood count (RBC), neutrophils, and lymphocytes counts, or in the hemoglobin and hematocrit. Only a few weak correlations (r < 0.21) were found between these hematological parameters and the measures of serum clozapine and nor-clozapine. CONCLUSIONS: The mechanism of clozapine-induced hematotoxicity at the therapeutic dosage range is probably not by direct toxicity of clozapine or nor-clozapine to the blood cells or their precursors. The formation of the cytotoxic nitrenium compound from clozapine by neutrophils may be necessary.

Adolescent↗