The absolute bioavailability of HB 420 (a new pharmaceutical form of glibenclamide) was investigated in comparison with an i.v. infusion of glibenclamide and also in comparison with HB 419 (Semi-Euglucon) on a group of 10 healthy volunteers with the aid of a highly specific bioanalytical detection method. A comparison of the dose-corrected areas under the concentration-time curves yielded an absolute bioavailability of 102% for HB 420. The relative bioavailability of HB 419 to HB 420 was 73%. This resulted in a bioequivalent dosage relationship of 2.5 mg HB 419 to 1.75 mg HB 420. It could be experimentally confirmed on further 10 healthy volunteers that 1.75 mg HB 420 (identical with Semi-Euglucon N) and Semi-Euglucon (containing 2.5 mg HB 419) are bioequivalent with respect to the absorbed quantity of active agents. The differences in absorption rate between the new and the old form did not lead to relevant differences in the glucose profile and the release of insulin, so that the two forms can be regarded as being pharmacodynamically equivalent. The median for the terminal elimination half-life for glibenclamide was 1.38 hours (min. 0.65, max. 4.64 hours), the total clearance was 100 ml/min and the steady-state distribution volume was 7.3 l (0.1 l/kg). On the basis of half-life, it can be expected that the elimination of the unchanged substance will be virtually complete within 10-12 hours. During long-term therapy, however, it cannot be ruled out that in some diabetics cumulation could occur, the cause of which cannot be explained by the data presented.

Download full-text PDF

Source

Publication Analysis

Top Keywords

absolute bioavailability
12
healthy volunteers
8
175 420
8
0
5
bioavailability bioequivalence
4
glibenclamide
4
bioequivalence glibenclamide
4
semi-euglucon
4
glibenclamide semi-euglucon
4
semi-euglucon absolute
4

Similar Publications

Prebiotics as modulators of colonic calcium and magnesium uptake.

Acta Physiol (Oxf)

February 2025

Institute for Molecular Medicine, Health and Medical University Potsdam, Potsdam, Germany.

Ca and Mg are essential nutrients, and deficiency can cause serious health problems. Thus, lack of Ca and Mg can lead to osteoporosis, with incidence rising both in absolute and age-specific terms, while Mg deficiency is associated with type II diabetes. Prevention via vitamin D or estrogen is controversial, and the bioavailability of Ca and Mg from supplements is significantly lower than that from milk products.

View Article and Find Full Text PDF

Hepatic impairment (HI) trials are traditionally part of the clinical pharmacology development to assess the need for dose adaptation in people with impaired metabolic capacity due to their diseased liver. This review aimed at looking into the data from dedicated HI studies, cluster these data into various categories and connect the effect by HI with reported pharmacokinetics (PK) properties in order to identify patterns that may allow waiver, extrapolations, or adapted HI study designs. Based on a ratio ≥ 2 or ≤ 0.

View Article and Find Full Text PDF

Preclinical pharmacokinetics, absolute bioavailability and dose proportionality evaluation of bioactive phytochemical Withanone in rats.

Bioorg Chem

January 2025

Pharmaceutics & Pharmacokinetics Division, CSIR-Central Drug Research Institute, Lucknow 226031, India; Academy of Scientific and Innovative Research (AcSIR), Ghaziabad 201002, India; Institute of Cancer Therapeutics, School of Pharmacy and Medical Sciences, Faculty of Life Sciences, University of Bradford, Bradford BD7 1DP, United Kingdom. Electronic address:

Withanone (WN), a bioactive phytochemical isolated from the medicinal herb Withania somnifera, has shown multiple pharmacological and therapeutic successes, including neuroprotective and anti-cancer activities. However, detailed pharmacokinetic (PK) properties of pure WN were not well defined. Pharmacokinetic (PK) characteristics, dose proportionality, and absolute bioavailability of pure WN were explored in rats using an efficient, reliable, and sensitive LC-MS/MS assay to address this gap.

View Article and Find Full Text PDF

Toxicity Risk Assessment of Clethodim Enantiomers in Rats and Mice: Insights from Stereoselective Effects.

J Agric Food Chem

January 2025

School of Pharmaceutical Sciences, Liaoning University, 66 Chongshan Road, Shenyang 110036, Liaoning Province, P. R. China.

Clethodim is a chiral herbicide with two enantiomers. The herbicidal activity of (-)-clethodim is 1.3-2.

View Article and Find Full Text PDF

Pharmacokinetics of cisplatin in the systemic versus hyperthermic intrathoracic or intraperitoneal chemotherapy.

Cancer Chemother Pharmacol

December 2024

Department of Oncology, Tangdu Hospital, The Air Force Medical University, No.569 Xinsi Road, Xi'an, Shaanxi Province, 710038, China.

Objective: To compare the pharmacokinetics and adverse effects of cisplatin administered via intravenous infusion for systemic chemotherapy (SC) versus injection into the perfusate during hyperthermic intrathoracic chemotherapy (HITHOC) or hyperthermic intraperitoneal chemotherapy (HIPEC).

Methods: Total 60 patients who received SC, HITHOC, or HIPEC in the Department of Oncology, Tangdu Hospital, were enrolled into this study. After administering same dose of cisplatin (40 mg) via either intravenous infusion (SC group) or injection into the perfusate during the HITHOC or HIPEC procedure, concentration of cisplatin in the plasma as well as in the hyperthermic perfusate at various time points was quantified by HPLC analysis.

View Article and Find Full Text PDF

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!