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Biomedical subjects

M E Teresi

Publications and source records attributed to M E Teresi.

9 recordsLinked to original sources

Apparent decrease in population clearance of theophylline: implications for dosage.

BACKGROUND: Having observed in recent years that the theophylline dose requirements needed to attain peak serum concentrations of 10 to 20 micrograms/ml infrequently reached previously described mean values, we hypothesized that a downward shift in the range of dose requirements had occurred among patients with asthma. STUDY DESIGN: We examined dosage requirements needed to attain peak serum concentrations of 10 to 20 micrograms/ml in all patients with chronic asthma treated with theophylline by the Pediatric Allergy and Pulmonary Clinic at the University of Iowa from 1990 to 1994 (n = 300) and at the Pediatric Pulmonary Clinic at the University of Florida from 1992 to 1995 (n = 93). We then compared these doses to previous dose requirements from 1978 to 1983 determined in the same manner. RESULTS: Despite similar mean peak serum concentrations during both time periods (14 micrograms/ml), mean theophylline dosage requirements during the period of this study were approximately 25% lower among all age groups than those previously observed (p < 0.001). There were no significant differences in mean dosage requirements between the Iowa and Florida patients in any age group examined. CONCLUSIONS: Theophylline dose requirements needed to attain serum concentrations of 10 to 20 micrograms/ml have decreased significantly from those on which current dosing recommendations are based. This suggests a decrease in mean clearance of the population.

Adolescent

Attitudes of healthcare professionals toward patient counseling on drug-nutrient interactions.

OBJECTIVE: To evaluate the attitudes of healthcare providers on drug-nutrient interaction (DNI) counseling. DESIGN: A mail survey. SETTING: Random sample of healthcare providers with interest in nutrition, practicing in Iowa or Nebraska. METHODS: A 48-item questionnaire was constructed on the basis of a review of DNI literature. The survey was sent to 100 pharmacists, 50 registered dietitians, 25 registered nurses, and 25 physicians identified from culled mailing lists of the American Society of Parenteral and Enteral Nutrition and the Iowa Nebraska Society of Parenteral and Enteral Nutrition. Assessed variables included the amount of DNI counseling provided, who is in the best position to provide DNI counseling, and what information should be included in instructional materials on DNIs for patients. Data were entered into a relational database for evaluation and comparison. RESULTS: The usable response rate was 49.5 percent (n = 99): 49 pharmacists, 29 dietitians, 18 nurses, and 3 physicians. Only 12 respondents provided DNI counseling in > 50 percent of patient interactions. Seventy-one respondents (72 percent) felt pharmacists were in the best position to discuss DNIs with patients. More than half of the respondents felt a new DNI pamphlet should be developed to replace an existing Food and Drug Administration-sponsored pamphlet. Although 70 percent felt the new pamphlet should be organized according to specific drugs, many felt the format should also include specific populations and disease states. Eighty-six percent indicated that a chart on DNIs geared toward healthcare professionals would be useful. CONCLUSIONS: Patient-oriented resources should be developed to enhance DNI counseling. Pharmacists are in a uniquely advantageous position to provide DNI counseling.

Attitude of Health Personnel

Ifosfamide-induced hyperpigmentation.

BACKGROUND: Pigmented banding of the nails and hyperpigmentation of hands and feet may occur during cyclophosphamide therapy. Ifosfamide, an analogue of cyclophosphamide, might be expected to cause similar pigmentary changes, but, to the knowledge of the authors, there are no reports of this. METHODS: The authors describe skin pigment changes in a 5-year-old patient receiving ifosfamide, MESNA, and etoposide for the treatment of relapsed Wilms tumor. RESULTS: A review of the literature concerning cyclophosphamide-induced pigmentary changes is presented, along with a discussion of the possible correlation of renal dysfunction with pigmentary changes. CONCLUSIONS: This case should alert health care providers to this uncommon adverse effect of ifosfamide.

Child, Preschool

Bioequivalence of two methotrexate formulations in psoriatic and cancer patients.

OBJECTIVE: To compare the bioequivalence of a generic methotrexate (MTX) tablet (Mylan) with that of a brand-name (Lederle) product. DESIGN: A single-dose, randomized, crossover study. SETTING: Clinical Research Center (CRC) at a university hospital. PATIENTS: Men and women who had a diagnosis of malignancy or psoriasis who were at least 21 years old. METHODOLOGY: Two overnight study periods were scheduled at the CRC at least one week, but not more than two weeks apart. Each period consisted of a 10-hour fast prior to and 4 hours following oral MTX 15 mg administered as six 2.5-mg tablets. Blood samples were collected over 48 hours. Plasma MTX concentrations were determined using an HPLC assay. Area under the curve from zero to infinity (AUC0-infinity) was calculated by the log-trapezoidal method. RESULTS: Twenty-two patients (21 psoriasis, 1 colon cancer) aged 23-61 years completed both study periods. Mean values for peak concentration, time to peak concentration, and AUC0-infinity were 0.80 mumol/L, 1.2 hours, and 3.0 mumol.h/L, respectively, for Mylan's MTX tablets and 0.81 mumol/L, 1.4 hours, 3.0 mumol.h/L, respectively, for Lederle's MTX. Normalization for weight or body surface area did not affect interpatient variability. Relative bioavailability of generic MTX was 99.2 percent. Rate and extent of absorption were not significantly different and the confidence intervals were within the range of 80-120 percent required by the Food and Drug Administration. CONCLUSIONS: Mylan's MTX tablet is bioequivalent to Lederle's product.

Adult

Excretion of hydroxyurea into milk.

This article documents that hydroxyurea (HUR) is excreted into human breast milk, and it reviews the literature describing similar evaluations for other antineoplastic agents.

Adult

Methotrexate bioavailability after oral and intramuscular administration in children.

Although methotrexate is one of the most commonly used drugs for maintenance therapy in childhood acute lymphocytic leukemia (ALL), its oral absorption is highly variable and its intramuscular bioavailability at dosages used for ALL therapy has not been assessed in children. We therefore determined the absolute bioavailability of orally and intramuscularly administered methotrexate in 12 pediatric patients receiving 13 to 120 mg/m2 methotrexate every week as maintenance therapy for ALL. Mean bioavailability, as determined by comparing the area under the concentration-time curve after oral or intramuscular administration with that produced by the same dosage given intravenously, was 33% (range 13% to 76%) for oral (n = 11) and 76% (54% to 112%) for intramuscular (n = 7) administration (P less than 0.01). Median bioavailability (with orally administered dosages less than or equal to 40 mg/m2 (range 13 to 40 mg/m2) was 42% (19% to 76%); at dosages greater than 40 mg/m2 (43 to 76 mg/m2), bioavailability was significantly lower, 17.5% (12.7% to 22.3%, p less than 0.02). Conversely, there was no significant relationship between dosage and bioavailability with intramuscularly administered drug. The substantially higher bioavailability for intramuscularly injected methotrexate may warrant its consideration as an alternative to oral administration, especially for dosages greater than 40 mg/m2.

Administration, Oral

Simultaneous administration of multiple model substrates to assess hepatic drug clearance.

We have evaluated a method to simultaneously assess three major processes involved in hepatic drug clearance using three model substrates administered simultaneously as a 5-minute intravenous injection. Lorazepam, indocyanine green, and antipyrine are used to assess conjugation, liver blood flow, and microsomal oxidative metabolism, respectively. These substrates were administered individually and as a mixture to 10 healthy adult male volunteers to determine if clearances of any of the compounds were affected by simultaneous administration. Mean clearances of the substrates were not different when administered alone (9.97, 0.78, and 0.53 ml/min/kg) vs. together (11.5, 0.89, and 0.52 ml/min/kg), using a paired t test. Since we were using this method to assess hepatic drug clearance in children with leukemia, the effect of short-term allopurinol was assessed. The three model substrates were administered to the volunteers after 0, 1, 8, and 22 days of treatment with allopurinol, 200 mg t.i.d. There was no change in mean clearance of any of the three compounds at any point during allopurinol treatment (repeated-measures ANOVA). We conclude that this technique is a simple and valid method to simultaneously assess three major processes involved in hepatic drug clearance and is not affected by up to 22 days of oral allopurinol treatment. This simple technique, requiring a single set of blood samples, has potential applications in the assessment of developmental changes in hepatic drug clearance, as well as the effects of environmental, therapeutic, and pathophysiologic factors on three major processes involved in hepatic drug clearance.

Administration, Oral

Pharmacokinetics of anticancer drugs in children.

Interpatient pharmacokinetic variability normally observed in adults is often of even greater magnitude in paediatric patients because of age-related maturation of physiological processes responsible for drug disposition. Several antineoplastic agents have shown age-related changes, including alterations in volume of distribution, hepatic (doxorubicin, cyclophosphamide), and renal (bleomycin, methotrexate) clearances. These differences in pharmacokinetics as a function of age alter systemic exposure to chemotherapy, and may alter the efficacy and toxicity profile for standard doses of antineoplastic drugs. The relationship of systemic exposure to toxicity has been most clearly defined for methotrexate. Clinical monitoring of methotrexate serum concentrations, and adjustment of folinic acid dosages and duration of rescue based on methotrexate disposition is now routine. More recently, pharmacodynamic data have been published for high-dose methotrexate, epipodophyllotoxins, cisplatin, and cytarabine (cytosine arabinoside), indicating a relation between drug disposition and toxicity or efficacy. Collectively, these data suggest that the pharmacokinetics of many anticancer drugs in children is different from adults, and that variability in drug disposition may have an important influence on toxicity or efficacy.

Adult

Evaluation of a noninstrumented disposable method for quantifying serum theophylline concentrations.

STUDY OBJECTIVE: To compare the performance of a new point-of-care theophylline assay (AccuMeter) with that of a standard laboratory assay (TDx), and another point-of-care method (AccuLevel). DESIGN: Prospective evaluation of consecutive patients receiving theophylline. SETTING: University-based, ambulatory, allergy-pulmonary clinic. PATIENTS: Forty subjects receiving maintenance theophylline therapy for asthma. INTERVENTIONS: Theophylline concentrations obtained from AccuMeter, TDx, and AccuLevel were compared. MEASUREMENTS AND MAIN RESULTS: The error, or difference, between TDx and AccuMeter results in 40 subjects on maintenance theophylline described accuracy. Mean error, an estimate of bias, was 1.1 (95% CI 0.72-1.5), 0.67 (0.34-1.0), and 0.98 (0.79-1.2) microg/ml for AccuMeter capillary, serum, and heparinized blood samples. Square root of the mean squared error, an estimate of precision, was 1.6 (1.2-2.0), 1.22 (0.90-1.5), and 1.14 (0.96-1.3) microg/ml for AccuMeter capillary, serum, and heparinized samples. Difference between AccuMeter and AccuLevel ME, an estimate of relative bias, was 0.59 (0.04-1.1) microg/ml. The difference in mean squared errors, an estimate of relative precision, was 0.86 (-0.54-2.3) microg/ml. CONCLUSIONS: AccuMeter demonstrated good precision and minimal bias compared with TDx and AccuLevel . Method of sample collection had no effect on its accuracy.

Adolescent