Cross-over bioavailability studies

A phase I, open-label, randomized, cross-over study to investigate the bioavailability, safety, tolerability and pharmacodynamics following single oral administration of XYZ1234 as capsule and single intravenous administration of XYZ1234 in healthy men. 

Our first stereospedfic bioequivalence evaluation using verapamil formulations was a pilot study conducted in 24 healthy male volunteers. The study compared the bioavailability of two sustained-release dosage forms and an immediate release formulation of racemic verapamil in a three-way cross-over study. Table 2 summarizes the results observed for verapamil. Table 3 the results for norverapamil. First, pharmacokinetic... 

The in vivo bioavailability studies should generally be single dose, cross-over studies with administration under fasting conditions, of formulations with different release rates, and a reference solution. The primary response variable in bioavailability studies aimed at establishing IVIVCs is the assessment of an in vivo dissolution-time or an absorption-time profile. Further details regarding assessment of such data are given in the section Bioavailability Studies . The number of subjects to be included should be based on the desired precision in the mean estimate of the dissolution-time profile. 

Few drugs are given Intravenously. This means that for most drugs the fraction which is absorbed intact into the circulation is often very much less than unity. This fraction, F, is referred to as the bioavailability. The bioavailability of oral formulations is often established in special studies (usually cross-over studies in healthy volunteers) in which the area under the plasma - concentration time curve (AUC) of the oral formulation is compared with that of an intravenous formulation. The bioavailability can then be calculated as the ratio of AUC to dose delivered for the oral formulation to the corresponding ratio for the intravenous formulation. Since the total amount eliminated from the body is equal to the clearance times the AUC, and since the total amount eliminated equals the amount absorbed, which is simply the dose times the bioavailability, so dose, AUC, bioavailability and clearance are linked by the formula, F x Dose = Clearance x AUC. For many drugs the bioavailability and clearance are independent of the dose administered. This property is referred to as dose-proportionality and is... 

Repa inide. A three-period cross-over open-label study in healthy subjects found that nifedipine 10 mg daily decreased the maximum plasma level of repaglinide 2 mg three times daily hy 2.7% and increased the bioavailability of repaglinide by 11%, but this was not statistically significant. There was a higher incidence of adverse effects during concurrent use. ... 

Clarke, J.D., Hsu, A., Riedl, K., Bella, D., Schwartz, S. J., Stevens, J.F., and Ho, E. 2011. Bioavailability and inter-conversion of sulforaphane and emcin in human subjects consuming broccoli sprouts or broccoli supplement in a cross-over study design. Pharmacological Research, 64(5), 456-63. doi 10.1016/j.phrs.2011.07.005. 

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