Studies on pyrazinoylguanidine. 7. Effects of single oral doses in normal human subjects.

Abstract:

:In a three-phase study, single oral doses of placebo, followed in 1 week by pyrazinoylguanidine (PZG; 900 mg), followed in 3 weeks by pyrazinoic acid (PZA; 300 mg) were given to 8 normal male subjects. Blood analyses performed 0, 2 and 4 h after administration of placebo or drug revealed that compared to mean 0 h values, PZG and also PZA, but not placebo, decreased mean values for serum glucose, insulin, C-peptide, triglycerides and free fatty acids. In all groups, serum potassium, urea, fibrinogen, high-density lipoprotein and low-density lipoprotein were unchanged. PZA, but not PZG, increased serum uric acid. PZG significantly reduced very-low-density lipoprotein whereas PZA only tended to do so. PZG was well tolerated and without any side effect, but in 7 of the 8 normal volunteers, PZA produced a variable vasomotor response over the blush area of the face and neck lasting from 30 min in 3 subjects to 4 h in 1 subject. Collectively, these results suggest generally similar metabolic responses of normal subjects to PZG and PZA after only a single oral dose of each. Previously, it was unrecognized that acute administration of PZG and PZA could produce such rapid metabolic changes.

journal_name

Pharmacology

journal_title

Pharmacology

authors

Vesell ES,Beyer KH Jr

doi

10.1159/000028276

subject

Has Abstract

pub_date

1999-03-01 00:00:00

pages

140-6

issue

3

eissn

0031-7012

issn

1423-0313

pii

28276

journal_volume

58

pub_type

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