The relationship between the plasma concentration of free nicotinic acid and some of its pharmacologic effects in man

Svedmyr, N; Harthon, Lennart; Lundholm, Lennart

doi:10.1002/cpt1969104559

Cited by 59 publications

(20 citation statements)

References 5 publications

(6 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In contrast to this, we assessed no nicotinic acid-induced effects on blood pressure and pulse in a physiological dose range. Our results are confirmed by several other clinical trials with nicotinic acid in pharmacological doses in mice as well as in men (Spies et al 1938b;Svedmyr et al 1969;Benyo et al 2005;Menon et al 2007). Coming back to the receptor-mediated effects, in spite of the wide distribution of the GPR109A receptor in a large variety of immune cells and adipocytes, the release of prostaglandins as an answer to nicotinic acid-induced activation could only be observed in dermal Langerhans cells (Benyo et al 2006;Maciejewski-Lenoir et al 2006;Gille et al 2008).…”

Section: Discussionsupporting

confidence: 86%

Investigation of niacin on parameters of metabolism in a physiologic dose: randomized, double-blind clinical trial with three different dosages

Schweikart¹,

Reimann²,

Schön³

2009

International Journal of Food Sciences and Nutrition

View full text Add to dashboard Cite

The aim of this double-blind, placebo-controlled cross-over design trial was to assess the safety of a multi-vitamin preparation containing nicotinic acid in a physiological dose. Seventy-two healthy volunteers took part in this trial. At six consecutive time-points, we systematically documented blood pressure, pulse, skin temperature and flushing symptoms after an oral dose of up to 50.1 mg nicotinic acid. The results suggest that nicotinic acid in a dosage of 16.7 mg does not cause flushing symptoms. In higher doses up to 50.1 mg, flushing symptoms are sporadically possible. There was no physiologically relevant change regarding the central metabolic parameters blood pressure, pulse and skin temperature.

show abstract

Section: Discussionsupporting

confidence: 86%

Investigation of niacin on parameters of metabolism in a physiologic dose: randomized, double-blind clinical trial with three different dosages

Schweikart¹,

Reimann²,

Schön³

2009

International Journal of Food Sciences and Nutrition

View full text Add to dashboard Cite

show abstract

“…), which is gradually transformed to nicotinic acid resulting in a slow rise to lower plasma levels of nicotinic acid, does not produce a considerable FF A level overshoot (Carlson and Oro, 1969). A therapeutic concentration of nicotinic acid between 0.5 and 1.0].1g/ ml is needed for its action on lipolysis (Carlson et aI., 1968;Svedmyr et at., 1969) and a maximum effect may be seen well below 5/-1g!ml (Carlson and Oro, 1969).…”

Section: Relationship Between Dose (Concentration) and Effectmentioning

confidence: 93%

Clinical Pharmacokinetics of Hypolipidaemic Drugs

Gugler

1978

Clinical Pharmacokinetics

View full text Add to dashboard Cite

Since hypo/ipidaemic drugs are widely used, despite the still unanswered question whether lowering of plasma lipids has a protective effect on the development of atherosclerosis, discussion of the clinical pharmacokinetics of the main representatives of this group of drugs is warranted.Clofibrate is quantitatively transformed to its active metabolite, chlorophenoxyisobutyric acid (CPlB), immediately after oral administration. Absorption of CPlB is complete, but relatively slow with peak concentrations being attained 2 to 6 hours after the dose. The apparent volume of distribution is between 6 and 12 litres; plasma protein binding is higher than 90 % • but is reduced in the nephrotic syndrome. in renal failure. and in cirrhosis. The elimination half-life ofCPlB ranges between 10 and 25 hours, is shorter in patients with the nephrotic syndrome, but is prolonged in renal failure ill close c:urrelation with the degree of renal impairment. The plasma clearance of the total drug (mean of 7ml/min) appears to be increased in the nephrotic syndrome. but is decreased in renal failure and is unchanged in liver cirrhosis. Clearance of the unbound drug (mean of 240ml/ min) is markedly reduced in renal failure, but is also reduced in liver cirrhosis. No pharmacokinetic changes are observed in acute hepatitis. Urinary excretion of CPlB is normally 10 to 15 % of the dose; excretion is reduced in .renal failure, but is unaffected in the nephrotic syndrome and in liver cirrhosis.Nicotinic acid is rapidly absorbed with peak concentrations being attained after 45 minutes.The systemic availability is about 90 % . Accumulation of the drug is reported in red blood cells.but no information is available on its distribution and on its plasma protein binding. The plasma elimination half-life is about 45 minutes. One third of an oral dose is excreted in urine unchanged. With pharmacological doses the major metabolite is nicotinuric acid; other metabolites being N-methyl-nicotinamide, 2-pyridone.and 4-pyridone, respectively. A measurable pharmacological effect is achieved with plasma concentrations of 0.1 to 0.2pg/ml, while a therapeutic range of 0.5 to 1.0Jlg/ml is suggested. Flushing of the skin is reported to-occur only at the beginning of treatment when the plasma concentration of nicotinic acid increases. Several analogues of nicotinic acid have been developed with the intention of achieving a sustained effect by a gradual in vivo liberation of nicotinic acid. . Cholestyramine is not absorbed from the gastrointestinal tract. As it is an anion exchange resin it may interfere with the absorption of a number of drugs by binding them to the resin.~-Sitosterol absorption is normally less than 5 %. but has been 25% in 2 sisters. so that a genetically determined influence on absorption is assumed.

show abstract

“…19) If this be true of CS or RS, then the final concentration of niacin derived from the serum in the control medium that contains 10% CS or RS is estimated to be less than 0.04 mM. This concentration range is below 1/250 of 10 mM, which is the least effective dose of niacin, suggesting that niacin derived from serum might be negligible from the pharmacological point of view.…”

Section: )mentioning

confidence: 99%

Anti-Invasive Activity of Niacin and Trigonelline against Cancer Cells

Hirakawa

Okauchi

Miura

et al. 2005

Bioscience, Biotechnology, and Biochemistry

View full text Add to dashboard Cite

The relationship between the plasma concentration of free nicotinic acid and some of its pharmacologic effects in man

Abstract: Nicotinic acid was infused intravenously in healthy human beings in doses between

Cited by 59 publications

References 5 publications

Investigation of niacin on parameters of metabolism in a physiologic dose: randomized, double-blind clinical trial with three different dosages

Investigation of niacin on parameters of metabolism in a physiologic dose: randomized, double-blind clinical trial with three different dosages

Clinical Pharmacokinetics of Hypolipidaemic Drugs

Anti-Invasive Activity of Niacin and Trigonelline against Cancer Cells

Contact Info

Product

Resources

About