Determination of 1-(β-d-arabinofuranosyl)-5-(1-propynyl)-uracil and a metabolite, 5-propynyluracil, in plasma using ASTED (automated sequential trace enrichment of dialysates) combined, on-line, with high-performance liquid chromatography

Buick, A.R.; Sheung, C. T. C. Fook

doi:10.1016/0378-4347(93)80422-z

Cited by 11 publications

(6 citation statements)

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“…Examples of its application are the analysis of sulfonamides and selected other drugs in egg, meat, and milk (Aerts et al, 1988(Aerts et al, , 1991(Aerts et al, , 1995, anticonvulsants in plasma (Turnell and Cooper, 1987), uracil and its metabolites in plasma (Buick and Fook, 1993), and flumequine and oxolinic acid from fish tissues Thanh et al, 1990).…”

Section: Introductionmentioning

confidence: 98%

“…Although the ASTED technology has not previously been applied to FQs in eggs, its use has been reported for the isolation of FQs and other drug classes from various biological matrices. Examples of its application are the analysis of sulfonamides and selected other drugs in egg, meat, and milk (Aerts et al, 1988(Aerts et al, , 1991(Aerts et al, , 1995, anticonvulsants in plasma (Turnell and 1987), uracil and its metabolites in plasma (Buick and Fook, 1993), and flumequine and oxolinic acid from fish tissues (Andresen and Rasmussen, 1990;Thanh et al, 1990).…”

Section: Introductionmentioning

confidence: 99%

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Determination of Sarafloxacin Residues in Fortified and Incurred Eggs Using On-Line Microdialysis and HPLC/Programmable Fluorescence Detection

Maxwell

Cohen

Donoghue

1999

J. Agric. Food Chem.

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Isolation of sarafloxacin (SAR) from fortified and incurred chicken eggs was done by a combination of liquid-liquid extraction and aqueous on-line microdialysis performed on an automated trace enrichment of dialysates (ASTED) system. The ASTED system coupled a sample cleanup procedure with HPLC and programmable fluorescence detection. Overall recoveries of 87-102% for SAR were obtained from samples fortified over a range of 1-100 ng/g. The relative standard deviation values ranged from 22 to 26% for samples fortified between 1 and 5 ng/g and from 2 to 12% for samples fortified between 10 and 100 ng/g. The limits of detection and quantitation were 0.2 and 1 ng/g, respectively. Eggs containing incurred SAR, which were collected over a 3-day dosing period and for 5 consecutive days thereafter, also were analyzed by using this technique. Because the method is automated, 35 samples can be processed within a 24-h period, which enables large data sets to be acquired over a short time period.

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Section: Introductionmentioning

confidence: 98%

Section: Introductionmentioning

confidence: 99%

Determination of Sarafloxacin Residues in Fortified and Incurred Eggs Using On-Line Microdialysis and HPLC/Programmable Fluorescence Detection

Maxwell

Cohen

Donoghue

1999

J. Agric. Food Chem.

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“…Plasma and urine samples were stored at Ϫ20ЊC until assay by high-performance liquid chromatography (HPLC) for both 882C87 and the pyrimidine base 5PU (2). Plasma samples were pretreated by using an automated sequential trace enrichment of dialysates (ASTED) procedure to remove macromolecules by dialysis and to concentrate and clean up the sample before injection onto HPLC.…”

Section: Methodsmentioning

confidence: 99%

Pharmacokinetics and tolerability of single oral doses of 882C87, a potent, new anti-varicella-zoster virus agent, in healthy volunteers

Peck

Weatherley

Wootton

et al. 1995

Antimicrob Agents Chemother

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882C87 is a nucleoside analog with potent, specific activity against varicella-zoster virus. It is approximately seven times as potent as acyclovir with an in vitro 50% inhibitory concentration of 1 to 2 M. The tolerability and pharmacokinetics of single doses of 882C87 have been investigated in a series of studies with healthy young and elderly adult volunteers. The young received 50 to 1,600 mg, and the elderly received 50 and 100 mg. Concentrations of 882C87 and its main metabolite, the pyrimidine base 5-(1-propynyl)uracil (5PU), in plasma and urine were assayed by an automated sequential trace enrichment of dialysate-high-performance liquid chromatography procedure, and noncompartmental pharmacokinetic parameters were derived from the data. Concentrations of 882C87 in plasma increased proportionally for doses of up to 400 mg, but after higher doses the increase was less than dose proportional. In young adults, after 200, 400, and 1,600 mg, the maximum concentrations of the drug in plasma were 9.0, 16.3, and 34.7 M, respectively, and the areas under the concentration-time curve (AUC) from 0 h to infinity were 166.6, 333.7, and 822.9 M ⅐ h, respectively. Elimination half-life was 11.3 to 13.0 h after 50 to 400 mg, increasing to 15.3 h after 1,600 mg, associated with a small decrease in renal clearance. In healthy elderly volunteers concentrations of 882C87 in plasma after 50 and 100 mg were similar to those in young adults after twice the dose; apparent clearance and renal clearance were significantly reduced, and half-life was significantly longer at 15 h. Administration of 882C87 with food produced a small, nonsignificant reduction in mean AUC from 0 h to infinity, but in subjects with a low fasting AUC there was an increase after food and in subjects with a high fasting AUC there was a decrease. Concentrations of 5PU in plasma were one-third to one-half those of 882C87 and, in most subjects, were not dose proportional. There was a lag of at least 5 h after dosing with 882C87 before 5PU was detectable in plasma.The most effective treatment for shingles currently available is acyclovir (5, 9). However, after an oral dose of 800 mg, the mean concentration of the drug in plasma (C max ) is 7.5 M, which is below the concentration (IC 50 ) required to inhibit varicella-zoster virus (VZV) replication by 50% in vitro (5). Higher oral doses do not produce higher concentrations in plasma, and in addition, the short half-life (t 1/2 ) of acyclovir necessitates dosing five times a day. 1-(␤-D-Arabinofuranosyl)-5-(1-propynyl)uracil (882C87) (Fig. 1) is a thymidine analog under development as an alternative therapy for VZV infection. In plaque reduction assays in MRC-5 cells it has an IC 50 of 1 to 2 M against a range of VZV strains, making it approximately seven times more potent than acyclovir (7). It has a molecular weight of 282.25, pK a of 8.64, log P (octanolwater) of Ϫ1.02, and mean plasma protein binding (measured by centrifugal ultrafiltration) of 88% at plasma drug concentrations between 1 and 100 M (4). It has...

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“…detection at 290 nm, for both 882C87 and 5-PU [12]. Plasma samples were pretreated using an Automated Sequential Trace En-richment of Dialysates (ASTED) procedure to remove macromolecules by dialysis and to concentrate and clean up the sample.…”

Section: Plasma Drug Assaymentioning

confidence: 99%

“…All doses were given after an overnight fast. After the oral dose, blood samples were taken pre-dose and at 0.5, 1, 2, 3, 4, 5,6,7,8,10,12,15,18,24,32,48,72 and 96 h post dose and urine collected for 96 h, additional samples were taken at 15 and 45 min after the start of the intravenous infusion. Pulse and blood pressure were measured pre-dose, every 15 min during the i.v.…”

Section: Design Of Studiesmentioning

confidence: 99%

The bioavailability and disposition of 1‐(beta‐D‐arabinofuranosyl)‐5‐(1‐ propynyl)uracil (882C87), a potent, new anti‐varicella zoster virus agent.

Peck

Wootton

Lee

et al. 1995

Brit J Clinical Pharma

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1. The bioavailability and disposition of 882C87, an anti‐varicella zoster virus (VZV) agent, have been investigated in healthy young and elderly volunteers. 2. The mean bioavailability of a 200 mg tablet was 21.1% in the young (range 13.3‐33.0%, n = 10) and 24.6% in the elderly (range 14.4‐38.4%, n = 8), which is sufficient to achieve plasma concentrations well above the IC50 for anti‐VZV activity. 3. Plasma concentrations of 882C87 after 50 mg i.v. were higher in the elderly than in the young, associated with a significantly longer half‐life (13.7 vs 11.8 h) and decreased renal clearance (0.11 vs 0.14 ml min‐1 kg‐1) and total clearance (0.15 vs 0.17 ml min‐1 kg‐1). 4. After intravenous administration, the main route of elimination of 882C87 was renal with 81.6% recovered unchanged in urine in the young and 71.2% in the elderly. The pyrimidine base, 5‐propynyluracil (5‐PU) was unquantifiable in plasma and only present in trace amounts in urine. 5. After oral administration to four healthy volunteers, only 17% of a dose of [14C]‐882C87 was recovered unchanged in urine and 58% as 5‐PU, with total recovery in urine accounting for 86% of the dose. There was a lag of 4‐12 h before the appearance of 5‐PU in plasma, peak concentrations were one‐third to a half those of 882C87. The data suggest that 5‐PU is formed from unabsorbed 882C87 in the gut lumen and then absorbed and excreted in urine. 6. 882C87 is a potential once daily treatment for shingles.

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Determination of 1-(β-d-arabinofuranosyl)-5-(1-propynyl)-uracil and a metabolite, 5-propynyluracil, in plasma using ASTED (automated sequential trace enrichment of dialysates) combined, on-line, with high-performance liquid chromatography

Cited by 11 publications

References 4 publications

Determination of Sarafloxacin Residues in Fortified and Incurred Eggs Using On-Line Microdialysis and HPLC/Programmable Fluorescence Detection

Determination of Sarafloxacin Residues in Fortified and Incurred Eggs Using On-Line Microdialysis and HPLC/Programmable Fluorescence Detection

Pharmacokinetics and tolerability of single oral doses of 882C87, a potent, new anti-varicella-zoster virus agent, in healthy volunteers

The bioavailability and disposition of 1‐(beta‐D‐arabinofuranosyl)‐5‐(1‐ propynyl)uracil (882C87), a potent, new anti‐varicella zoster virus agent.

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