Effect of doses on the bioavailability of phenytoin from a prompt-release and an extended-release preparation: single dose study
Rojanasthien, N.; Chaichana, N.; Teekachunhatean, S.; Kumsorn, B.; Sangdee, C.; Chankrachang, S.
Journal of the Medical Association of Thailand 90(9): 1883-1893
2007
ISSN/ISBN: 0125-2208 PMID: 17957935 Document Number: 2986
Objective: To determine the effect of doses on the bioavailability of a prompt-release and an extended-release phenytoin capsule after given as single doses. Material and Method. Eight healthy male volunteers were given single oral doses of 100, 200, and 300 mg of a prompt-release preparation (Ditoin((R))) and an extended-release phenytoin (Dilantin Kapseals((R))) preparation in a crossover design with a two weeks washout period after an overnightfast. Serial blood samples were collected over 72 h post-dose. Plasma phenytoin concentrations were determined by HPLC and pharmacokinetic parameters were analyzed by non-compartmental model. Results: Rate of phenytoin absorptionftom theprompt-release preparation was moreprolonged after the 300mg dose (7(max) 4.5 h) than those ofthe 100- and200-mg doses (T-max 3.5 and 3 h, respectively). Similarly, the T-max ofthe 200- and the 300-mg extended-release preparation (5.5 and 4 h) were moreprolonged than the 100-mg dose (3 h). Bioequivalence analysis showed that the C-max of all doses of the prompt-release preparation were higher than those values of the extended-release preparation with the mean C-max ratio (90% CI) of 1.32 (1.241. 40), 1.26 (1.14-1.40), and 1. 29 (1.10-1.51) for the 100-, 200- and 300-mg doses, respectively. The extent of absorption (A UC0-infinity) of 100-mg phenytoin was bioequivalent between the two preparations [mean A UC ratio (90% Q of 1. 15 however, for higher doses, the prompt-release products produced higher bioavailability than the extended-release products [mean AUC ratio (90% CI) of 1.19 (1.07-1.33) and 1.17 (0.98-1.38), respectivelyfor the 200- and 300-mg doses]. The difference in the bioavailability did not affect the elimination of phenytoin and their half-lives were comparable (11-13 h). Conclusion: The bioavailability of phenytoin from both preparations increased proportionally over the dose range of 100-306 mg, however, the bioavailability of the prompt-release preparation was higher than the corresponding doses of the extended-release product.
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