In vitro rat hepatic metabolism of n-alkanes: nonane, decane, and tetradecane.
Jet propellant 8 (JP-8) jet fuel is a complex mixture of aromatic and aliphatic hydrocarbons. The aim of this study was to determine in vitro metabolic rate constants for semivolatile n-alkanes, nonane (C9), decane (C10), and tetradecane (C14), by rat liver microsomal oxidation. The metabolism was assessed by measuring the disappearance of parent compound by gas chromatography. Various concentrations of n-alkanes were incubated with liver microsomes from adult male F-344 rats. Nonlinear kinetic constants for nonane and decane were V(max) (nmol/mg protein/min) = 7.26 +/- 0.20 and 2.80 +/- 0.35, respectively, and K(M) (micro M) = 294.83 +/- 68.67 and 398.70 +/- 42.70, respectively. Metabolic capacity as assessed by intrinsic clearance (V(max)/K(M)) was approximately four-fold higher for nonane (0.03 +/- 0.005) than for decane (0.007 +/- 0.001). There was no appreciable metabolism of tetradecane even with higher microsomal protein concentration and longer incubation time. These results show a negative correlation between metabolic clearance and chain length of n-alkanes. These metabolic rate constants will be used to update existing physiologically based pharmacokinetic (PBPK) models for nonane and decane as part of developing a PBPK model for JP-8.
Department of Pharmaceutical and Biomedical Sciences, College of Pharmacy, University of Georgia, Athens, Georgia, USA. satheesh.s.anand@usa.dupont.com
Sathanandam S
SS
Anand
Jerry L
JL
Campbell
Jeffrey W
JW
Fisher
D000473:Alkanes / Q000032:analysis / Q000493:pharmacokinetics*; D000818:Animals; D002849:Chromatography, Gas; D004305:Dose-Response Relationship, Drug; D008297:Male; D008862:Microsomes, Liver / Q000378:metabolism*; D008954:Models, Biological; D051381:Rats; D011916:Rats, Inbred F344
D000473:Alkanes; C024713:n-tetradecane; C012867:decane; C017573:nonane