Al. Davis et al., APPLICATION OF A SIMPLIFIED METHOD TO DETERMINE BIOAVAILABILITY OF ANORAL DOSE OF PHENYTOIN, Journal of pharmacokinetics and biopharmaceutics, 21(2), 1993, pp. 195-208
The bioavailability of capsules of phenytoin was determined by two met
hods: a method involving the numerical integration of the Michaelis-Me
nten equation and an alternative method involving fitting the time cou
rse of plasma concentrations, following the administration of the refe
rence intravenous dosage, to an empirical quadratic function of time.
The latter procedure requires much simpler computations. The two metho
ds yielded very similar estimates of the rate and extent of absorption
of phenytoin. Total absorption was 0.90 +/- 0.05 and 0.89 +/- 0.05(x
+/- SE, n = 6) using the methods of numerical integration and quadrati
c curve fitting, respectively. Both methods indicated that the rate of
absorption of phenytoin was inconsistent and slow. Half the total abs
orption of phenytoin occurred over 2.5 +/- 0.3 hr but the remainder wa
s absorbed very slowly over a period of about 30 hr. Empirical functio
ns may be more generally useful in the determinations of the bioavaila
bility of drugs, particularly if some aspects of the disposition are s
aturable.