Accession Number : ADP008777


Title :   Pharmacokinetics of Niacinamide in Blood and Skin of Hairless Guinea Pigs


Corporate Author : ARMY MEDICAL RESEARCH INST OF CHEMICAL DEFENSE ABERDEEN PROVING GROUND MD


Personal Author(s) : Bongiovannieier, R ; Koplovitz, I ; Shulz, S ; Lieb, J ; Railer, R


Full Text : https://apps.dtic.mil/dtic/tr/fulltext/u2/p008777.pdf


Report Date : 13 May 1993


Pagination or Media Count : 11


Abstract : Niacinamide (NA) has been reported to be effective in reducing the development of microblisters caused by sulfur mustard (HD) vapor exposure in the Hairless guinea pig when given as a single bolus pretreatment 30 min prior to HD vapor exposure (Yourick et al.). The purpose of these experiments was to establish the pharmacokinetics of NA in the hairless guinea pig to optimize the evaluation of NA against HD cutaneous injury. A high performance liquid chromatography (HPLC) method was developed for the quantitation of NA in blood and skin. The method was linear (corr coeff r = 0.998) and sensitive with a working range from 50 microns/ml to 2000 microns/ml. The NA Tl/2 was measured after a bolus injection of 750 and 375 mg/kg via IP and IV routes, respectively. The Tl/2 was 2.8 + or - 0.3 hr for both routes. Drug concentrations in blood, during multiple dosing (5 IP) of a fixed dose (375 mg/kg, i.p.) given every 2.8 hr, were within 15% of the theoretical values calculated using a computer model (Principle of Superposition). NA serum levels ranged from 325 microns/mL to 1404 microns/mL (n = 12). The corresponding skin levels were within 93% of the blood levels. The elimination of NA from the skin paralleled its elimination from the blood. The results of these studies will aid in the future evaluation of NA as a pretreatment/treatment for HD injury.


Descriptors :   *ANTIDOTES , *PHARMACOKINETICS , *SKIN(ANATOMY) , *BLOOD , *HD AGENT , MODELS , COMPUTERS , VAPORS , LIQUID CHROMATOGRAPHY , DOSAGE , WOUNDS AND INJURIES , VALUE , SULFUR , DRUGS , ELIMINATION , CHROMATOGRAPHY , GUINEA PIGS


Subject Categories : Toxicology
      Pharmacology
      Chemical, Biological and Radiological Warfare


Distribution Statement : APPROVED FOR PUBLIC RELEASE