Search PubMed⌕ Search

Biomedical subjects

G Peter

Publications and source records attributed to G Peter.

At least 55 records · Page 3Linked to original sources
PubMed1992

Streptococcal pharyngitis: current therapy and criteria for evaluation of new agents.

Penicillin has been the recommended drug of choice in most cases of group A streptococcus (GAS) pharyngitis for nearly 40 years based on its efficacy in the prevention of acute rheumatic fever. Since trials of other drugs for the prevention of rheumatic fever are no longer feasible in the United States, eradication of GAS pharyngitis has become the surrogate for their evaluation. On the basis of this criterion, specific therapeutic regimens have been recommended, and numerous other drugs have gained approval as alternatives to penicillin. Current therapeutic issues include possible decreased efficacy of penicillin, timing of the initiation of therapy, and drugs of choice for patients whose treatment fails, who are chronic carriers, or who have frequent infections. Criteria for assessment of new drugs include clinical response, likelihood of prevention of rheumatic fever, rates of relapse and recurrent infection, and drug safety. The establishment of uniform guidelines and definitions of response for new drug evaluations by the Infectious Diseases Society of America should aid in the further assessment of new antibacterial agents as therapy for GAS pharyngitis. However, no data yet suggest that any of these drugs should replace penicillin as the drug of choice.

Anti-Bacterial Agents↗
PubMed1991

Metabolic fate of the novel antihypertensive drug naftopidil.

The metabolism of 14C-naftopidil ((R,S)-1-(2-methoxyphenyl)-1-piperazinyl-3- (1-naphthyl-oxy-2-propanol, CAS 57149-07-2) and the pharmacodynamic action of the metabolites was investigated. The metabolic pathway in rat, dog, mouse and man was qualitatively similar, with preference for the hydroxylation of the phenyl or naphthyl moiety of naftopidil [phenyl)hydroxy-metabolite, (naphthyl)hydroxy-metabolite). Cleavage of the parent compound and production of the propylene glycol metabolite was a further important reaction especially for rat and man. In all species investigated, demethylation of naftopidil occurs to a minor extent. O-desmethyl-naftopidil, (phenyl)hydroxy-naftopidil and (naphthyl)hydroxy-naftopidil were found to have similar affinities for the alpha 1-adrenoceptors as the parent compound (IC50)nmol/l): 433.0; 585.0; 52.7; respectively; naftopidil: 235.0). The naftopidil metabolites, like the parent compound showed no alpha 2- or beta-adrenoceptor affinity.

Animals↗
PubMed1991

Pharmacokinetic fate of the novel antihypertensive drug naftopidil.

The pharmacokinetics of naftopidil (R,S)-1-[4-(2-methoxyphenyl)-1-piperazinyl]-3-(1-naphthyloxy)-2 propanol, CAS 57149-07-2) was studied in rats and dogs using 14C-labeled drug in pharmacodynamically effective doses (oral doses: 5/10 mg/kg and intravenous doses: 1/2.5 mg/kg in rats/dogs, respectively). Naftopidil (14C) was rapidly and in high extent absorbed in rats and dogs after oral administration. The absolute bioavailability of the parent compound amounted to 9% in rats and indicates a high first pass effect to in part pharmacodynamically effective metabolites, as was shown in a previous paper. The parent compound and its 14C-metabolites were widely distributed into the periphery, more pronounced in the rat than in the dog, as indicated from comparison of the volumes of distribution and dose corrected Cmax- and AUC0-infinity-values in plasma. Elimination of radioactivity from plasma occurred in rat and dog in a similar rate. Tissue distribution studies in the rat showed highest peak-concentrations in the gastrointestinal (GI) tract (evaluated with contents) due to the predominant biliary elimination, followed by liver, adrenals, pituitary and Harderian glands, lungs, pancreas, kidneys, adipose tissue, bone marrow, aorta, thyroid and lymph nodes. Radioactivity was eliminated from most of the tissues within the first 168 h. Highest fractions of the dose were detected--apart from the GI-tract--in liver, muscle, skin, blood, and kidneys. After repeated administration to rats, accumulation of radioactivity in the 28 tissues examined did not exceed factor 9 or factor 5 in most of the tissues.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗
PubMed1990

Radioreceptor assay for the determination of alpha 1-adrenoceptor-binding material in rat plasma following single oral administration of naftopidil.

Naftopidil could be characterized by receptor binding studies as an alpha 1-adrenergic antagonist with a binding affinity constant (Ki) of 58.3 nmol/l. both enantiomers of naftopidil revealed similar values, indicating no stereoselective inhibition of 3H-prazosin-binding. An alpha 1-adrenergic radiorecptor assay (RRA) was developed to determine receptor-binding material (parent compound and active metabolites) in the plasma of rats following single oral administration of naftopidil (50 mg/kg). The results indicate a rapid absorption. At the first sampling time (0.5 h) maximum concentration of receptor-binding material was measured. Terminal half-life was calculated with 16.7 h.

Administration, Oral↗
PubMed1989

Independence of enhanced protein catabolism from glucocorticoids in chronically uremic rats.

Patients with chronic renal failure are prone to develop negative nitrogen balance resulting clinically in wasting and malnutrition. To study the role of glucocorticoids in the pathogenesis of uremic catabolism, we determined urinary excretion rates of urea and Nt-methylhistidine in chronically uremic rats with and without RU 38486, a potent antiglucocorticoid. In comparison to pair-fed non-uremic animals, chronically uremic rats displayed significantly enhanced ureagenesis, as demonstrated by increased urinary urea excretion, and myofibrillar protein breakdown, as indicated by increased excretion rates of urinary Nt-methylhistidine. The administration of RU 38486 to chronically uremic rats, however, did not result in a normalization of urinary excretion of Nt-methylhistidine. Similarly, the antiglucocorticoid did not influence the extent of ureagenesis in our uremic animals, as it was demonstrated by comparable levels of urinary urea excretion. This suggests that glucocorticoids are not involved in the pathogenesis of enhanced catabolism in chronic renal insufficiency.

Animals↗
PubMed1989

Catabolic effects of ethanol in chronically uremic rats.

Both ethanol consumption and uremia are considered to be associated with wasting, malnutrition and debilitation. The present study was designed to investigate as to whether ethanol exerts a stimulatory effect on the catabolic state of renal failure. Rats underwent 5/6-nephrectomy and were fed either with or without ethanol. The degree of uremia was comparable in both groups. Ethanol-fed uremic rats, however, displayed higher serum levels of urea (+ 103%) and glucose (+29%), as compared to uremic animals without alcohol. Subsequently, the urea N appearance was enhanced (+60%) in uremic rats with alcohol as compared to uremic animals without alcohol. In sham rats urea N appearance was also increased (+39%) following ethanol administration in comparison to sham-operated rats without alcohol, albeit to a lesser degree. Urinary Nt-methylhistidine excretion, an indicator of myofibrillar protein breakdown, was enhanced throughout the experiment in uremic rats receiving ethanol. Finally, ethanol caused higher urinary excretion rates of corticosterone in uremic animals as compared to uremic rats without ethanol. There was a significant correlation between urinary corticosterone excretion and both urea N appearance and urinary Nt-methylhistidine excretion. We conclude that ethanol consumption further aggravates the catabolic state of uremia and that this is mediated by an increment in glucocorticoid production.

Alcohol Drinking↗