Development of antibody — mediated extraction followed by GC/MS (antibody/GC/MS) and its application to iloprost determination in plasma

Krause, W.; Jakobs, U.; Schulze, P.; Nieuweboer, B.; Hümpel, M.

doi:10.1016/0262-1746(85)90104-0

Cited by 35 publications

(5 citation statements)

References 14 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The aim of the present study was to examine in elderly volunteers the rates and routes of excretion of iloprost and its metabolites using radiolabeled drug, and to compare the plasma levels of the parent compound with those measured previously using antibody separation/GC/MS [11]. Metabolite patterns were also determined and were compared with those found in the rat.…”

Section: -Inyl]-bicyclomentioning

confidence: 97%

“…The pharmacokinetics of iloprost using the radiolabeled drug has been investigated in the rat [6,7], dog [8], monkey [9] and cat [10]. In man, pharmacokinetic data have been obtained using antibody-mediated extraction of iloprost from plasma, followed by GC/MS quantitation [11]. In healthy young volunteers, iloprost exhibited a biological half-life of approximately 0.5 h and, in contrast to prostacyclin, it was bioavailable after oral administration.…”

Section: -Inyl]-bicyclomentioning

confidence: 99%

See 1 more Smart Citation

Pharmacokinetics and pharmacodynamics of radio-labeled iloprost in elderly volunteers

Krause¹,

Krais²

1987

Eur J Clin Pharmacol

Self Cite

View full text Add to dashboard Cite

The plasma levels and excretion of tritium-labeled iloprost in healthy elderly male and female volunteers have been measured after i.v. infusion of 2 ng X kg-1 X min-1 for 4 h and oral administration of 0.1 and 0.48 microgram/kg. During infusion, a steady-state of labeled compounds in the plasma was not achieved. Total radioactivity declined from a mean of 408 pg equiv/ml in three phases, with half-lives of 24 min, 1.7 h and 5.0 h, respectively. A steady-state of unchanged iloprost was reached rapidly with a peak of 81 pg/ml. Plasma levels declined biphasically with half-lives of 6 min and 31 min. Total clearance was 24 ml X min-1 X kg-1. Maximum concentrations of labeled substances after oral administration were 307 and 1,051 pg equiv/ml after 29 and 39 min, respectively. The peak of unchanged iloprost (116 pg/ml) was observed 7.5 min after an oral dose of 0.48 microgram/kg. Bioavailability was 16%. Iloprost was totally metabolized and the metabolites were mainly excreted in urine. The main biotransformation products in plasma and urine were tentatively identified by cochromatography as dinor- and tetranoriloprost and their glucuronides. ADP-induced platelet aggregation was reduced by 60% during the i.v. infusion and 15 min after oral administration of 0.48 microgram/kg. Heart rate and blood pressure were virtually unaffected. Common side-effects were facial flush, headache and nausea.

show abstract

Section: -Inyl]-bicyclomentioning

confidence: 97%

Section: -Inyl]-bicyclomentioning

confidence: 99%

Pharmacokinetics and pharmacodynamics of radio-labeled iloprost in elderly volunteers

Krause¹,

Krais²

1987

Eur J Clin Pharmacol

Self Cite

View full text Add to dashboard Cite

show abstract

“…After sodium dodecyl sulfatepolyacrylamide gel electrophoresis,28 the gel was washed in 0.25% Triton X-100, overlaid on a fibrin plate, and incubated for 16 hours.27 Plasminogen activators were identified as areas of lysis on the fibrin gel detected both by protein staining and by dark-ground illumination. Iloprost concentrations were determined by a modification of the method of Krause et al 29 Briefly, iloprost was extracted from plasma along with an internal standard, deuterated iloprost, with an affinity column containing an antiiloprost antibody coupled to Sepharose as the stationary phase. The extracted iloprost was derivatized with pentafluorobenzyl bromide and bis(trimethylsilyl)-trifluoroacetamide.…”

Section: Biochemical Analysismentioning

confidence: 99%

Pharmacokinetics of tissue-type plasminogen activator during acute myocardial infarction in men. Effect of a prostacyclin analogue.

et al. 1992

View full text Add to dashboard Cite

BACKGROUND Coronary reocclusion complicates the thrombolytic therapy of acute myocardial infarction despite the routine use of aspirin. This is consistent with experimental studies demonstrating that multiple agonists, in addition to thromboxane A2, mediate the platelet activation underlying reocclusion. Consequently, a more potent antiplatelet therapy with a broader spectrum of activity than aspirin may be required in this setting. Prostacyclin and its more stable analogue, iloprost, inhibit platelet aggregation to all known agonists and exert an additional effect over aspirin alone. Experiments in animal models have demonstrated, however, that iloprost increases the clearance of tissue-type plasminogen activator (t-PA) and impairs thrombolysis in vivo. This study examines whether a similar interaction occurs in humans. METHODS AND RESULTS Twelve patients with acute myocardial infarction received t-PA intravenously, 60 mg in the first hour and a maintenance infusion of 13.3 mg/hr for 3 hours. Patients were assigned in a double-blind fashion to iloprost (2 ng/kg/min) or placebo following the initial 90 minutes of the maintenance infusion of t-PA. Iloprost decreased mean arterial blood pressure (-10 +/- 2.9 mm Hg, p less than 0.05) but did not alter heart rate. Steady-state plasma iloprost concentration was 591 +/- 64 pmol/l. At this concentration, iloprost markedly inhibited platelet aggregation in vitro, particularly in the presence of aspirin. Steady-state clearance of t-PA was unchanged by iloprost (454 +/- 65 versus 443 +/- 136 ml/min in controls, p = NS). Furthermore, neither elimination kinetics nor plasma protein binding of t-PA was altered by iloprost. CONCLUSIONS At plasma levels that exert a potent antiplatelet effect, iloprost did not alter the pharmacokinetics of t-PA in men. Prostacyclin analogues may prove useful as an adjunct to plasminogen activators, particularly in patients at high risk for thrombotic reocclusion.

show abstract

“…Thromboxane 8 2 (TXB 2 ) and its 2,3 dina r metabolite were analysed in 10 ml aliquots of urine that had been spiked with 5 mg 2 H• TXB 2 and 2,3 dinar TXB 2 inLem al standards. These urine samples were purified by extraction onto immunoaffinity columns labelled with an antibody to TXB 2 , with a high (>60%) cross-reactivity for 2,3 dinor TXB 2 [16]. The thromboxane metabolites were eluted with 95% acetone and the eluate evaporated to dryness under N 2 • The residue was subsequently derivatized to the d-trifluoro methyl benzyl -trimethylsilyl derivative and analysed by gas ~chromatography, negative ion chemical ionization mass spectrometry on a Finnegan 4500, monitoring M/Z -585 and -589 for TXB 2 and M/Z -557 and -561 for its 2,3 dinor metabolite and deuterated standards, respectively.…”

Section: Measurements Of Thromboxane B 2 and 23 Dinor Thromboxane B 2...mentioning

confidence: 99%

Effects of nonsteroidal anti-inflammatory drugs on the bronchial hyperresponsiveness of middle-aged male smokers

Lim¹,

Turner²,

Watson³

et al. 1990

Eur Respir J

View full text Add to dashboard Cite

Bronchial hyperresponsiveness (BHR) in smokers is believed to be a consequence of airway wall inflammation. We have examined the effects of treatment with nonsteroidal anti-inflammatory drugs (NSAID) on BHR to inhaled histamine, measured as the provocative concentration reducing forced expiratory volume in one second (FEV1) by 20% (PC20), in middle-aged male cigarette smokers in two separate double-blind, placebo-controlled, cross-over trials. Baseline FEV1 in these smokers ranged from 41-117% predicted values. In the first study 15 men (mean age 58 yrs, FEV1 2.20 l) were examined before and one hour after a single dose of 1.2 g aspirin. There was no significant change in PC20 (geometric mean 1.88 mg.ml-1 pre-aspirin, 1.89 mg.ml-1 post-aspirin) or baseline FEV1 and we observed no tachyphylaxis to the effects of inhaled histamine at one hour after placebo. In the second study 10 men (mean age 60 yrs, FEV1 2.53 l) were examined before and after three days' treatment with the NSAID flurbiprofen 50 mg t.d.s. Baseline PC20 was higher in this group than in the first study. There was no relationship between the excretion of urinary thromboxane metabolites and the intensity of BHR under baseline conditions; flurbiprofen greatly reduced the urinary excretion of thromboxane metabolites, but baseline FEV1 was not altered. Analysis of change in PC20 was complicated by a difference in baseline PC20 before the two treatments, but treatment with flurbiprofen did not significantly attenuate BHR. The results suggest that thromboxane or other cyclo-oxygenase products of arachidonic acid metabolism do not play an important role in the short-term maintenance of BHR to histamine in middle-aged male cigarette smokers.

show abstract

Development of antibody — mediated extraction followed by GC/MS (antibody/GC/MS) and its application to iloprost determination in plasma

Cited by 35 publications

References 14 publications

Pharmacokinetics and pharmacodynamics of radio-labeled iloprost in elderly volunteers

Pharmacokinetics and pharmacodynamics of radio-labeled iloprost in elderly volunteers

Pharmacokinetics of tissue-type plasminogen activator during acute myocardial infarction in men. Effect of a prostacyclin analogue.

Effects of nonsteroidal anti-inflammatory drugs on the bronchial hyperresponsiveness of middle-aged male smokers

Contact Info

Product

Resources

About