Table 4.

Summary of F, Fa, Fg, and Fh Values for UGT Substrates in Humans ¹.

Name	F	Fa	Fg	Fh	UGTs Involved	Intestinal Metabolism? 2	Reference
Canagliflozin	0.65	1 3	0.75 4	0.86	UGT1A9, UGT2B4	No	Devineni et al. [94]
Dapagliflozin	0.78	1 3	0.90	0.86	UGT1A9, UGT2B7	Yes	Boulton et al. [97]
Diclofenac	0.54	1 3	0.64	0.85	UGT2B7, UGT1A9, UGT1A6, UGT2B15	Yes	Varma et al. [90]
Ertugliflozin	1.05	1.11	1.08	0.88	UGT1A9, UGT2B4, UGT2B7	Yes	Raje et al. [98]
Gemfibrozil	0.98	1 3	1.09	0.90	UGT2B7	Yes	Nishimuta et al. [20]
Lorazepam	0.93	1 3	0.97	0.96	UGT2B4, UGT2B7, UGT2B15	Yes	Varma et al. [90]
Raloxifene	0.02	0.63	0.054	0.593	UGT1A1, UGT1A8, UGT1A9, UGT1A10 5	Yes	Mizuma [12]
Troglitazone	0.45	1 3	0.56	0.80	UGT1A1, UGT1A10	Yes	Nishimuta et al. [20]
Lorazepam	0.93	1 3	0.97	0.96	UGT2B4, UGT2B7, UGT2B15	Yes	Varma et al. [90]
Telmisartan	0.43	0.90	0.75	0.64	UGT1A1, UGT1A3, UGT1A9	Yes	Varma et al. [90]
Oxazepam	0.93	0.93	1.01	0.99	UGT1A9, UGT2B7, UGT2B15	Yes	Varma et al. [90]

¹ Numbers were either taken as reported or calculated using the approach of Kharasch et al. [89], reported Fa (or assumed 1 in the absence of a reported value), and a liver blood flow rate of 1.5 L/min [99]. F = bioavailability, Fa = fraction absorbed, FDp = fraction of dose passing into the portal vein, Fg = fraction of drug escaping first-pass intestinal metabolism, and Fh = hepatic availability. ² Based on UGT expression in intestine from Basit et al. [8]. ³ Fa was assumed to be 1. In this case the Fg actually represented FDp (= Fa × Fg). ⁴ Canagliflozin Fg is most likely underestimated, since UGT1A9 and UGT2B4 are not expressed in the intestines. ⁵ For raloxifene, SULT1E1 contributes to metabolism, but intestinal metabolism is thought to be mainly due to glucuronidation by UGT1A1, 1A8, and 1A10 [100].