21) Clin Pharmacol Ther.1969 Jul-Aug;10(4):559-70.

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

Svedmyr N, Harthon L, Lundholm L.

Abstract

Nicotinic acid was infused intravenously in healthy human beings in doses between 0.01 and 0.1 mg. per kilogram per minute for 20 to 180 minutes. The relationship between pharmacologic action and blood concentration of nicotinic acid was investigated. An increase of free nicotinic acid in plasma by 0.1 to 0.4 µg per milliliter was accompanied by increased blood flow through the hand, which maximally amounted to 75 per cent, and a 100 per cent increase in blood flow through the muscle. The pulse rate increased, but there was no change in blood pressure. The blood concentrations of free fatty acids and glucose decreased. Flushing of the face and neck persisted as long as the plasma nicotinic acid increased but disappeared when a constant level was reached. The intensity of the remaining pharmacologic effects were only initially correlated to the flushing. A fivefold increase of the dose of infused nicotinic acid (0.05 to 0.07 mg. per kilogram per minute) induced a proportional increase of the plasma concentration. The muscle blood flow was considerably increased (200 per cent) by the higher dose, but the other effects were not significantly changed. The total concentration of pyridine compounds in whole blood increased during the infusion, parallel with plasma nicotinic acid, but decreased more slowly than the free nicotinic acid after the infusion, still being elevated when the pharmacological effects had disappeared. The mechanism of the vasodilating effect of nicotinic acid is discussed.