Although the effects of endocrine dysfunction on drug metabolism have been well explored in experimental animal models, corresponding data for humans with endocrine disorders are scanty. Thyroid dysfunction has been associated with altered metabolism of some drugs and of some endogenous compounds as well. Hypothyroidism increases the half-life of antipyrine, digoxin, methimazole, and some β blockers, whereas hyperthyroidism has the opposite effect. A few clinical studies in diabetic patients indicate no apparent impairment of drug metabolism, although impairment has been noted in diabetic rats. Malfunctions of the pituitary, adrenal cortex, and gonads markedly reduce hepatic drug metabolism in rats. On the basis of these findings, it may be supposed that such disorders could significantly affect drug metabolism in humans. However, until sufficient evidence is obtained from clinical studies in patients, such extrapolations must be considered tentative.
Finally, the release of inflammatory mediators, cytokines, and nitric oxide associated with bacterial or viral infections, cancer, or inflammation are known to impair drug metabolism by inactivating P450s and enhancing their degradation.
Bailey DG, Dresser G, Arnold JMA: Grapefruit and medication interactions: Forbidden fruit or avoidable consequences? Can Med Assoc J 2013;185:309. Benowitz NL: Pharmacology of nicotine: Addiction, smoking-induced disease, and therapeutics. Annu Rev Pharmacol Toxicol 2009;49:57.
Clayton TA et al: Pharmacometabonomic identification of a significant hostmicrobiome metabolic interaction affecting human drug metabolism. Proc Natl Acad Sci USA 2009;106:14728.
Correia MA: Human and rat liver cytochromes P450: Functional markers, diagnostic inhibitor probes and parameters frequently used in P450 studies. In: Ortiz de Montellano P (editor): Cytochrome P450: Structure, Mechanism and Biochemistry, 3rd ed. Kluwer Academic/Plenum Press, 2005.
Correia MA, Hollenberg PF: Inhibition of cytochrome P450 enzymes. In: Ortiz de Montellano P (editor): Cytochrome P450: Structure, Mechanism and Biochemistry, 4th ed. Springer International, 2015.
Correia MA, Ortiz de Montellano P: Inhibition of cytochrome P450 enzymes. In: Ortiz de Montellano P (editor): Cytochrome P450: Structure, Mechanism and Biochemistry, 3rd ed. Kluwer Academic/Plenum Press, 2005.
Daly AK: Pharmacogenetics and human genetic polymorphisms. Biochem J 2010;429:435.
Guengerich FP: Human cytochrome P450 enzymes. In: Ortiz de Montellano P (editor): Cytochrome P450: Structure, Mechanism and Biochemistry, 4th ed. Springer International, 2015.
Guengerich FP: Role of cytochrome P450 enzymes in drug-drug interactions. Adv Pharmacol 1997;43:7.
Hustert E et al: The genetic determinants of the CYP3A5 polymorphism. Pharmacogenetics 2001;11:773.
Ingelman-Sundberg M: Pharmacogenetics: An opportunity for a safer and more efficient pharmacotherapy. J Intern Med 2001;250:186.
Ingelman-Sundberg M et al: Influence of cytochrome P450 polymorphisms on drug therapies: Pharmacogenetic, pharmacoepigenetic and clinical aspects. Pharmacol Ther 2007;116:496.