A purified, size-homogeneous (100 kDa), desialylated form of a truncated, soluble form of the epidermal growth factor receptor secreted by A431 human tumor cells has been found, by isoelectric focusing in immobilized pH gradients, to consist of two major isoforms (with pIs of 6.96 and 6.71), one intermediate form (pI 6.45) and a number (> 10) of minor components. The two major components have been purified to charge homogeneity by isoelectric focusing in a multicompartment electrolyzer with buffering isoelectric membranes having the following pI values: 5.90, 6.63, 6.76, 6.92, 7.05 and 7.35. Such single pI species are presently used for attempts at crystal growing.

ErbB Receptors↗

PubMedDate not supplied

Value of tumor localization in patients with insulinoma.

Based on our patient material, preoperative localization of insulinoma was correct with sonography in 13 (61.9%) of 21 patients, with computed tomography in 3 (21.4%) of 14 patients, with computed tomography with bolus injection of contrast medium in 11 (73.3%) of 15 patients, with angiography in 20 (66.6%) of 30 patients, and with percutaneous transhepatic portal vein catheterization with selective measurement of insulin in 10 (76.9%) of 13 patients. Intraoperatively, 40 (95.2%) of 42 insulinomas were palpable and 12 of 16 insulinomas were identified during intraoperative sonography. Although 95.2% of the insulinomas can be palpated, we would support additional diagnostic localization since it may improve the reliability of palpation.

Adenoma, Islet Cell↗

PubMedDate not supplied

Steady state investigation of possible pharmacokinetic interactions of moxonidine and glibenclamide.

The aim of the study presented here was to determine possible pharmacokinetic interactions of moxonidine and glibenclamide at steady state in 18 healthy male volunteers. Multiple oral doses of 0.2 mg of moxonidine b.i.d. (q. 12 h) and of 2.5 mg of glibenclamide o.i.d. (q. 24 h) were administered alone and in combination in an open, non-randomized, three-treatment design. The preparations were given for 5 days in each of the 3 periods. The results of this multiple dose study did not indicate substantial pharmacokinetic interactions of the drugs. Regarding the influence of glibenclamide on the pharmacokinetics of moxonidine, no significant changes were seen at all. In the presence of moxonidine, a minor decrease of bioavailability of glibenclamide was detectable, as could be derived from the AUC and clearance data. The actual differences were small and not considered to be of clinical significance.

Administration, Oral↗

PubMedDate not supplied

Absolute bioavailability of moxonidine.

In a randomized 2-way cross-over study with eighteen healthy male volunteers, two moxonidine preparations (tablets, treatment A vs. intravenous solution, treatment B) were tested to investigate absolute bioavailability and pharmacokinetics of moxonidine. The preparations were administered as single doses of 0.2 mg; prior to and up to 24 h after administration blood samples were collected and the plasma moxonidine concentrations determined. Urine samples were collected prior to and at scheduled intervals up to 24 h after administration for the determination of unchanged moxonidine. Moxonidine plasma and urine concentrations were determined by a validated gas chromatographic/mass spectrometric method with negative ion chemical ionization. The mean areas under the plasma concentration/time curves were calculated as [mean +/- standard deviation] 3438 +/- 962 pg.h/ml (AUC(0----Tlast)) and 3674 +/- 1009 pg.h/ml (AUC(0----infinity)) for treatment A; 3855 +/- 1157 pg.h/ml (AUC(0----Tlast)) and 4198 +/- 1205 pg.h/ml (AUC(0----infinity)) for treatment B. Mean peak plasma concentrations of 1495 +/- 646 pg/ml were attained at 0.56 +/- 0.28 h after oral treatment, mean peak plasma concentrations after intravenous treatment reached 3965 +/- 1342 pg/ml at 0.17 +/- 0.01 h (= coinciding with end of infusion). The mean terminal half-lives of moxonidine were derived as 1.98 h after administration of the tablet and as 2.18 h after infusion. The amounts of moxonidine excreted in urine during the 24 h following administration (Ae(24h)) in absolute figures and as percentage of the dose administered were 102 +/- 26 micrograms or 51 +/- 13% for the tablet and 122 +/- 33 micrograms or 61 +/- 16% for the infusion.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMedDate not supplied

Influence of food on the oral bioavailability of moxonidine.

Moxonidine is a new centrally acting anti-hypertensive with a very low adverse drug reaction profile. Among others, the aim of the study presented here was to determine the influence of food on the pharmacokinetics of moxonidine. Single oral moxonidine doses of 0.2 mg fasting and 0.2 mg non-fasting were administered in a randomized cross-over study. Eighteen subjects participated in the study, all of whom completed the study according to the protocol. Three sets of analytical plasma data could not be evaluated pharmacokinetically giving a total number of 15 evaluable cases. Renal excretion was evaluated for all 18 subjects. Food intake had no influence on the pharmacokinetics of moxonidine. The relative bioavailability of moxonidine administered under non-fasting conditions reached 94% of the bioavailability after fasted administration. Food intake resulted in a slight decrease of Cmax and a minimal increase of tmax as compared to the fasted treatment. The absorption half-life t1/2a showed a minor prolongation. These differences were not statistically significant in any of the parameters. For t1/2 lambda 2, CLtot and Ae(24h) no statistically significant differences were found between the fasting and non-fasting treatment. The amount of moxonidine excreted unchanged in urine accounted for about 46% of the dose administered after both treatments.

Administration, Oral↗