Bioavailability oral drugs

Veber DF, Johnson SR, Cheng H-Y, Smith BR, Ward KW, Kopple KD. Molecular properties that influence the oral bioavailability of drug candidates. J Med Chem 2002 45 2615-23. 

Agoram B, Woltosz WS and Bolger MB. Predicting the impact of physiological and biochemical processes on oral drug bioavailability. Adv Drug Deliv Rev 2001 50 Suppl l S41-67. 

Chan, O. H., Stewart, B. H. Physicochemical and drug-delivery considerations for oral drug bioavailability. Drug Discov. Today 1996, 1, 461 73. 

Veber, D., Johnson, S., Cheng, H., Smith, B., Ward, K., Kopple, K. D. Molecular properties that infiuence the oral bioavailability of drug candidates. /. Med. Chem. 2002, 45, 2615-2623. 

Select azole antifungals (e.g., itraconazole, voriconazole, and posaconazole) and the echinocandins are available for IA treatment. For initial therapy of IA, voriconazole had higher response and survival rates than c-AMB.102 An advantage of voriconazole is its 96% oral bioavailability, making use of this oral drug an attractive and less expensive alternative. The dose of voriconazole was 6 mg/kg IV every 12 hours for two doses, followed by 4 mg/kg IV every 12 hours for at least 7 days, at which time oral voriconazole 200 mg every 12 hours could be administered. Common toxicities reported with voriconazole include infusion-related, transient visual disturbances (i.e., blurred vision, altered color perception, photophobia, and visual hallucinations), skin reactions (i.e., rash, pruritus, and photosensitivity), elevations in hepatic transaminases and alkaline phosphatase, nausea, and headache.102 In addition, voriconazole increases the serum concentrations of medications cleared by cytochrome P-450 2C9, 2C19, and 3A4 (e.g., cyclophosphamide and calcineurin inhibitors) concomitant voriconazole-sirolimus should be avoided.103... 

Mandagere, A. K., T. N. Thompson, and K. K. Hwang. Graphical model for estimating oral bioavailability of drugs in humans and other species from their Caco-2 permeability and in vitro liver enzyme metabolic stability rates, J. Med. Chem. 2002, 45, 304-311... 

Chiou, W. L., Buehler, P. W., Comparison of oral absorption and bioavailability of drugs between monkey and human, Pharm. Res. 

Definition of Absorption and Bioavailability of Drugs following Oral Administration... 

Limited oral drug bioavailability may be explained by poor membrane permeability, low aqueous solubility in gastrointestinal fluids, or extensive first-pass metabolism in the gastrointestinal tract or liver. Successful lipophilic prodrugs... 

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