Table 2.

ADMET properties of these approved drugs.

Properties	Darunavir	Indinavir	Cidofovir	Sorivudine
Bioavailability	The absolute oral bioavailability of one single 600 mg dose of darunavir alone and with 100 mg of ritonavir twice a day was 37% and 82%, respectively. The bioavailability of oral darunavir is increased by about 30% when taken with food [55].	After oral administration, indinavir is rapidly absorbed in the fasting state (70%) [56].	Cidofovir has poor oral bioavailability (<5%) and is therefore administered intravenously [57].	BV-araU shows good bioavailability [58].
Distribution	Darunavir appears to bind to serum proteins, particularly α1-acid glycoprotein [59], 95% binding to plasma proteins [60].	Plasma protein binding of indinavir is approximately 60% [56].	Binding of cidofovir to plasma proteins is negligible (<7%) [57].	Found in plasma after oral administration [61].
Metabolism	Darunavir is extensively metabolized by CYP3A4 enzymes [60].	Indinavir undergoes extensive metabolism by cytochrome P-450-CYP3A4 isoenzymes [62,63].	Cidofovir is converted via cellular enzymes to the pharmacologically active cidofovir diphosphate [64].	Their metabolism in animals were higher [58].
Excretion	In healthy people, approximately 79.5% and 13.9% of the administered dose of radiolabeled darunavir was obtained in the feces and urine, respectively, when ritonavir was also added with it [55].	In healthy people, the proportion of eliminated unchanged indinavir in the urine was approximately 11% [65] and indinavir metabolites in the feces accounted for >47% [56].	Cidofovir is excreted extensively by the kidneys and is eliminated almost entirely as unchanged drug in the urine (>90% within 24 h) [66].	Higher Urinary excretion [58].
Toxicity	•Limited cytotoxicity [55]. •Drug-induced hepatitis (e.g. acute hepatitis, cytolytic hepatitis) has been reported with darunavir [55]. •Darunavir has not been studied in patients with renal impairment [55].	•No cytotoxicity was detected for indinavir prodrugs [67]. •Indinavir can cause transient and usually asymptomatic elevations in serum aminotransferase levels and mild elevations in indirect bilirubin concentration [68]. •Risk of acute renal failure [69].	•Risk of nephrotoxicity [66]. •Has carcinogenic potential based on animal studies [70]. •Absence of hepatotoxicity [71].	Shows lethal effect when co-administrated with 5-fluorouracil anti-cancer drugs [72].