PMID: 6432996Jul 1, 1984Paper

Pharmacokinetics of nitroglycerin after parenteral and oral dosing in the rat

Journal of Pharmaceutical Sciences
H L FungG A Maier

Abstract

The pharmacokinetics of nitroglycerin was characterized in detail using venous plasma after different intravenous bolus doses (0.15-2.48 mg/kg), intra-arterial infusion (8.2 micrograms/min over 5 h), and oral doses (7-100 mg/kg). Venous plasma clearance was found to be approximately 650 mL/kg and was independent of the intravenous or intra-arterial dose. This confirmed earlier reports that the venous plasma clearance of nitroglycerin in rats exceeded the value of normal cardiac output. A terminal half-life of approximately 15 min was observed after high intravenous bolus doses of nitroglycerin. This slow disappearance phase was likely rate limited by redistribution of drug back into the plasma. The bioavailability of oral nitroglycerin (F) showed an apparent Michaelis-Menten dependency on dose. F was less than 5% at doses less than 20 mg/kg, but increased to a plateau of approximately 20% from 50-100 mg/kg. First-pass metabolism of nitroglycerin is thus apparently controlled by at least two systems (sites or enzymes). Coadministration of mannitol hexanitrate, a potential competitive inhibitor of first-pass metabolism, did not increase F.

References

Mar 1, 1979·Circulation·J Y Wei, P R Reid
Jan 1, 1983·Annals of the New York Academy of Sciences·B E Pfingst, D Sutton
Jan 1, 1980·Therapeutic Drug Monitoring·W J Jusko, J Q Rose
Apr 1, 1981·Anesthesiology·A B HillJ K Denlinger

Citations

Sep 19, 2003·The Journal of Surgical Research·Ashish KhannaHo Leung Fung
Mar 1, 1985·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·A T BleiH L Fung
Jun 22, 1984·The American Journal of Medicine·H L Fung
Oct 1, 1993·Biopharmaceutics & Drug Disposition·T B Tzeng, H L Fung
Jul 25, 2020·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Kosta J PopovićIvan Čapo

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