Pharmacokinetics of intravenous glibenclamide investigated by a high performance liquid Chromatographic assay

Abstract

A simple high performance liquid chromatographic assay for the determination of plasma glibenclamide concentrations is described. This resolved glibenclamide from normal plasma constituents. The calibration curve of the assay was linear over the range 10-500 microgram/l and the minimum level of detection was 2 microgram/l. Within-assay coefficients of variation were 11.6% (20 microgram/l); 5.3% (50 microgram/l); 6.8% (100 microgram/l); between-assay coefficients of variation were 8.4% (20 microgram/l); 4.7% (50 microgram/l) and 7.4% (100 microgram/l). The assay was used to study the pharmacokinetics of a 1 mg intravenous dose of glibenclamide in eight normal subjects. The mean half-life was found to be 1.47 +/- 0.42 h (SD) and no evidence for a non-linear beta-phase or slowly equilibrating 'deep' compartment was found although this could not be rigorously excluded. The mean systemic drug clearance was 78 +/- 29 ml X h-1 X kg-1 and the apparent volume of distribution in the beta-phase was 155 +/- 44 ml/kg. The median time of maximum response of plasma immunoreactive insulin was 25 min and the median time of maximum blood glucose response was 53 min. No correlation could be found between the pharmacokinetics of glibenclamide and these responses in fasted normal individuals.

Pharmacokinetic and pharmacodynamic studies of glibenclamide in non‐ insulin dependent diabetes mellitus.

“…First, differing brands of glibenclamide have often been used and there is evidence that formulation may significantly affect bioavailability of the drug (Arnquist et al, 1983;Chalk et al, 1986;McEwen, 1984;Rupp et al, 1972). Some have studied glibenclamide entering the circulation so quickly that a rapid distribution phase could be confused with a first elimination half-life (Rogers et al, 1982). Second, some have studied normal subjects (Ings et al, 1981;Neugebauer et al, 1985;Sartor et al, 1980b), whilst others have, like ourselves, studied diabetic patients (Matsuda et al, 1983;Sartor et al, 1982) and the question may be raised as to whether the observed variations in drug handling reflect alterations in gastrointestinal motility secondary to autonomic neuropathy complicating the diabetic state (Ikegami et al, 1986).…”

“…Some studies have measured total radioactivity after giving radiolabelled drug (Balant et al, 1975;Rupp et al, 1972); others have determined immunoreactive glibenclamide (Balant et al, 1977) or employed high performance liquid chromatography (Rogers et al, 1982;WahlinBoll & Melander, 1979) or gas liquid chromatography (Castoldi & Tofanetti, 1979). Use of radioimmunoassay over-estimates glibenclamidederived plasma activity because of crossreactions with hydroxylated metabolites (Pearson, 1985).…”

“…Between challenges, the patients were maintained on glibenclamide 10-20 mg day-' Rogers et al (1982). Aliquots of plasma (1 ml) were mixed with 80 ,ul 1.3 M HCI to which were added 50 pLI of gliburnuride (10 ,ug ml-') as internal standard and 1 ml of distilled water.…”

Effect of pirprofen on glibenclamide kinetics and response.

“…Plasma glibenclamide concentrations in plasma were estimated by a high pressure liquid chromatographic technique (Rogers et al, 1982) with a minimum level of detection of2 ng ml-'and coefficients of variation of 11.6%, 5.3%, 6.8% at 20 ng ml-', 50 ng ml-l and 100 ng ml-l respectively. Blood glucose was determined by a glucose oxidase method (Trinder, 1969) and plasma immunoreactive insulin was estimated by a commercial radio-immunoassay kit (Lisophase, Lepetit, Milan, Italy).…”

Clinical Pharmacology of Sulfonylureas

“…The half-life obtained from intravenous data is between 1.2 and 2.5 h ROGERS et al 1982;NEUGEBAUER et al 1985;SPRAUL et al 1989;McEwEN et al 1982) and between 1.3 and 15 h after oral administration. Most studies obtained values of 1.5-5h (KARTIUNEN et al 1985;NEUGEBAUER et al 19X5;CHALK et al 1986;PEARSON et al 1986;SCHWINGHAMMER et al 1991).…”