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Biomedical subjects

N Ferencz

Publications and source records attributed to N Ferencz.

13 recordsLinked to original sources

Urinary excretion of 6-hydroxychlorzoxazone as an index of CYP2E1 activity.

OBJECTIVE: To determine whether the urinary excretion of 6-hydroxychlorzoxazone is an index of CYP2E1 activity in vivo. METHODS: Male volunteers (n = 27; age range, 17 to 36 years) who were abstinent from alcohol were studied. Chlorzoxazone, 500 mg, was given orally and plasma was collected at 31/2, 41/2, 51/2, and 61/2 hours after dosing. Urine was collected for 8 hours. Ten volunteers participated in full kinetic studies to define the absorption phase and plasma area under the concentration-time curve of chlorzoxazone and the urinary kinetics of the 6-hydroxy metabolite. Chlorzoxazone and the 6-hydroxy metabolite were measured by high-performance liquid chromatography. CYP2E1 activity was expressed as a hydroxylation index (HI = mmole oral chlorzoxazone dose/mmole 6-hydroxychlorzoxazone in 8-hour urine). RESULTS: There was a significant positive correlation between plasma elimination rate constant for chlorzoxazone (Ke) and urinary excretion of the metabolite (n = 27, r = 0.42, p < 0.03) and a significant negative correlation between plasma Ke and HI (n = 27, r = -0.41, p < 0.04). The mean absorption rate constant for chlorzoxazone of 3.11 +/- 4.67 hr-1 was fivefold greater than the plasma Ke of 0.57 +/- 0.17 hr-1 for the full kinetic studies. The formation clearance of the 6-hydroxy metabolite was negative between plasma Ke of the parent compound and disposition rate constant for urinary excretion of the 6-hydroxy metabolite (n = 15, r = 0.85, p < 0.0001). CONCLUSIONS: The urinary excretion of 6-hydroxychlorzoxazone is limited by formation rate and may be useful as an in vivo probe of CYP2E1 activity.

Adolescent↗

Comparative pharmacokinetics of two prodrugs of zidovudine in rabbits: enhanced levels of zidovudine in brain tissue.

The pharmacokinetics of two prodrugs of zidovudine (AZT), 1,4-dihydro-1-methyl-3-[(pyridylcarbonyl)oxy] ester and isoleucinyl ester (DPAZT and IAZT, respectively), were investigated in a rabbit model to determine their potential utility as drugs against human immunodeficiency virus. Drugs were administered by intravenous infusion over 5 min at doses equal to 10 mg of AZT per kg of body weight. The levels of the prodrugs and of released AZT in plasma, cerebrospinal fluid (CSF), and brain were determined by high-performance liquid chromatography analysis. DPAZT disappeared rapidly from plasma, whereas IAZT maintained a sustained level in plasma for up to 4 h. The levels in plasma of AZT released from DPAZT were consistently lower than the levels of AZT released from IAZT or AZT itself. At 75 min after infusion of AZT, DPAZT, and IAZT, the CSF plasma AZT ratios were 0.23, 0.30, and 0.25, while the brain/CSF AZT ratios were 0.32, 0.63, and 0.64, respectively. These results indicate that the administration of each of the prodrugs produced a higher concentration of AZT in the brain than did the direct administration of AZT. Both prodrugs therefore may be superior to AZT itself with respect to achieving anti-human immunodeficiency virus concentrations within the central nervous system.

Animals↗

Pharmacokinetics and long-term tolerance to ribavirin in asymptomatic patients infected with human immunodeficiency virus.

Single-dose and steady-state pharmacokinetics of the antiviral agent ribavirin were studied in seven male, asymptomatic, human immunodeficiency virus-seropositive subjects. After a single 400 mg intravenous infusion, mean terminal plasma half-life (t1/2) was 27.1 hours, mean volume of distribution was 802 L, and mean total plasma clearance was 26.1 L/hr. Renal clearance was 39% of total clearance and it exceeded creatinine clearance. Oral bioavailability was 44.6%. With long-term dosing (400 mg orally twice a day) ribavirin accumulated, reaching steady state in 2 to 4 weeks in plasma and red blood cells. Red blood cell concentrations greatly exceeded plasma concentrations (60:1). Plasma concentrations at steady state (trough) were 10- to 14-fold higher than the corresponding single-dose concentrations. The terminal t1/2 (washout) after 16 weeks greatly exceeded the t1/2 observed after a single oral dose (151 versus 29.6 hours). Ribavirin-induced reductions in hemoglobin ranging from 0.8 to 3.5 gm/dl were well tolerated. There was no significant reduction in CD4 lymphocytes during treatment with ribavirin for 16 weeks in subjects who had more than 200 CD4 cells at entry and who also remained free of opportunistic infections during 24 weeks of observation.

Administration, Oral↗

Creating standard treatment protocols: an analysis of pharmacy charges as an aid in their development.

A method for selecting DRG categories that have the potential for greatest pharmacy cost savings is described for a 400-bed, urban medical center. Seven variables describing the overall hospital costs and the specific pharmacy charges for 252 patients categorized under the four most prevalent DRGs observed over a 7-month period were examined. The DRG for chronic obstructive pulmonary disease was found to have the highest mean value for four of the seven variables and thus was selected as the first DRG for which to develop a standard treatment protocol. Preliminary progress in the design of pharmacy services within the standard treatment protocol are discussed.

Analysis of Variance↗

Building a structured learning package.

Pharmacists must become educators of patients and of pharmacy technical personnel. The literature cited in this paper has found that problems of patient compliance, personnel management, the high cost of medical care, and patient medical self-help may very well be solved in part through the application of competently written learning packages. One specific approach to learning package creation is illustrated in this paper, using the training of a unit-dose technician as an example. The subjects of student motivation, step-wise learning using subobjectives, learning feedback, material relevance, and student evaluation are discussed. Higher-level cognitive skills and readability are briefly discussed and illustrated to focus the readers' attention on the more difficult aspects of building learning packages.

Drug Information Services↗

Behavioral objectives for a hospital pharmacy residency program.

The purpose and design of behavioral objectives in educational programs are reviewed, and the behavioral objectives of a pharmacy residency program are listed. The behavioral objectives for the program follow, as a guide, the ASHP Accreditation Standard for Pharmacy Residency in a Hospital.

Accreditation↗