Subject oral bioavailability

The first-pass effect has not been extensively evaluated in infants and children. The maturational rate of metabolic pathways would be directly related to the oral bioavailability of a drug subject to first-pass effect. Drugs that undergo glucuronidation during en-terohepatic recirculation may have altered systemic availability in children up to approximately 3 years of age because of delayed maturation of conjugation. 

Fig. 18.7. Oral bioavailability of saquinavir with and without CFJ [42], Saquinavir (600 mg three capsules of Invirase, 200 mg each tablet) was administered to eight healthy male subjects (average body weight 76 kg) before and after consumption of two glasses (200 mL each) of CFJ at 15 and 45 min before drug administration. QMPRPIus was used to estimate human effective permeability (0.93 X 10-4 cm s 1), pure aqueous water...

Swabb EA, Sugerman A, Stern M Oral bioavailability of the monobactam aztreonam (SQ 26,776) in healthy subjects. Antimicrob Agents Chemother 1983 23 548-550. 

Absorption - Although well absorbed orally, naltrexone is subject to significant first-pass metabolism with oral bioavailability estimates ranging from 5% to 40%. Following oral administration, naltrexone undergoes rapid and nearly complete absorption with approximately 96% of the dose absorbed from the Gl tract. Peak plasma levels of naltrexone and 6- -naltrexol occur within 1 hour of dosing. 

Losartan - Compared with healthy subjects, the total plasma clearance in patients with hepatic insufficiency was about 50% lower and the oral bioavailability was about 2 times higher. A lower starting dose is recommended. 

The intravenous curve is, by definition, a representation of 100% bioavailability as the drug was put in its entirety into the vein. The oral curve has an area under it approximately 75% the size of the intravenous curve, and this suggests that 25% of the oral dose failed to get into the circulation. The oral bioavailability of the drug is the proportion getting into the vascular compartment, and can be measured if there is an intravenous dose curve available for the same subject at the same dose. In this example, F (the fraction bioavailable) is 0.75. It might be as high as 1.0 (100%) for some steroids, or as low as 0.1 (10%) or even less for poorly absorbed aminoglycosides. 

Budesonide is a potent synthetic analog of prednisolone that has high affinity for the glucocorticoid receptor but is subject to rapid first-pass hepatic metabolism (in part by CYP3A4), resulting in low oral bioavailability. A controlled-release oral formulation of budesonide (Entocort) is available that releases the drug in the distal ileum and colon, where it is absorbed. The bioavailability of controlled-release budesonide capsules is approximately 10%. 

Pharmacokinetic properties The compound is subject to an intensive first-pass metabolism via glucuronidation of the free phenolic hydroxyl group (Wilson et al., 1995 Strain et al., 1996). This strongly reduces oral bioavailability and induces a short duration of action. 

However, the food-effect study on Sporaffooral solution in healthy subjects observed that oral bioavailability of itraconazole actually decreased by 31 % under fed condition (Van de Velde et al., 1996). Thus, in its product labeling, it is indicated that SporShoral solution should be taken without a meal to ensure maximal absorption. Further, Spof Dcad solution and capsules should not be used interchangeably. 

C. Falcoz, A. Mackie, J. McDowall, J. McRae, L. Yogendran, G. Ventresca, and A. Bye, Oral bioavailability of fluticasone propionate in healthy subjects, Br. J. Clin. Pharmacol. 47 459P (1996). 

Pantoprazole is subject to low first-pass hepatic extraction, as reflected in an estimated absolute oral bioavailability of 77%. On repeated oral administration, the pharmacokinetics of pantoprazole (20 and 40 mg once daily) are similar to those after single dose administration [1,18]. The absolute bioavailability was 70% in patients with severe liver cirrhosis, and more than 90% in healthy elderly subjects [18]. 

The SAR around pazopanib 1 was extensively investigated by Harris and co-workers15 at GlaxoSmithKline (GSK). Pazopanib (1) was found to be the most potent member in the series with excellent in vitro activities against all the human VEGFR receptors. Moreover it exhibited good oral bioavailability of 72%, 65%, and 47%, when dosed at 10, 5 and 1 mg/kg in human subjects, respectively. 

Few pharmacokinetic studies are carried out beyond the range of 28-40 years and, consequently, there are few data on oral bioavailability for extremes of age. Gastric fluid is less acidic in newborns than in adults, which can affect the absorption of ionizable and acid-labile drags. Neonates are also associated with a leaky epithelium, which permits the absorption of proteins and other macromolecules not normally absorbed from the GI tract. Decreased enzymatic activity, including hepatic first-pass metabolism, is associated with the elderly, which may result in an increased oral bioavailabiliy for drags subject to the first-pass effect. 

Frohna P, Lu J, Eppler S, et al. Evaluation of the absolute oral bioavailability and bioequivalence oferlotinib, an inhibitor of the epidermal growth factor receptor tyrosine kinase, in a randomized, crossover study in healthy subjects. J Clin Pharmacol 2006 46(3) 282-90. 

Disposition in the Body. The absorption of digoxin after oral administration is variable and subject to bioavailability differences absorption occurs mainly in the small intestine and is... 

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