Bioequivalence and Bioavailability Forum

Hi Steven,

❝ And Blenchard et al. published 1983 that abs. BA is 108.3% in N=6. Hm, admittedly there should be better publications on this, but looks like complete absorption to me.

IMHO, F > 1 is not surprising. F > 1 is reported for theophylline, another methylxanthine (references from the 1980s somewhere in my pile; n = 12?). These are the rare examples where we have complete absorption and a first-pass metabolism in the lung. Hence, concentrations after an oral dose are higher than after IV because the pulmonary circulation is bypassed and there is no first-pass metabolism in the liver.

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Edit: Found them; the usual suspects…

1. Upton RA, Sansom L, Guentert TW, Powell JR, Thiercellin J-F, Shah VP, Coates PE, Riegelman S. Evaluation of the Absorption from 15 Commercial Theophylline Products Indicating Deficiencies in Currently Applied Bio­avail­ability Criteria. J Pharmacokin Biopharm. 1980; 8(3): 229–42. doi:10.1007/BF01059644.
   • As common in the 1980s, n = 12.
     From the Abstract:
     The alcoholic elixir surprisingly gave rise to a significantly greater (114 ± 14%, mean ± SD) amount absorbed than did the intravenous dose. The aqueous solution (99 ± 8%) and intravenous dose were statistically indistinguishable in this respect…
2. Steinijans VW, Schulz H-U, Böhm A, Beier W. Absolute Bioavailability of Theophylline from a Sustained-Release Formulation Using Different Intravenous Reference Infusions. Eur J Clin Pharmacol. 1987; 33: 523–6.
   • Two studies (n=12 in each), different infusion rates. Fast infusion F 100% (95% nonparametric CI: 89–115%), slow infusion F 88% (73–105%). In ten subjects F >100%; maximum 141%!