Absorption of phenytoin from rectal suppositories formulated with a polyethylene glycol base.

Autor: Burstein AH; Department of Pharmacy Practice and Sciences, University of Maryland, Baltimore, USA., Fisher KM, McPherson ML, Roby CA
Jazyk: angličtina
Zdroj: Pharmacotherapy [Pharmacotherapy] 2000 May; Vol. 20 (5), pp. 562-7.
DOI: 10.1592/phco.20.6.562.35157
Abstrakt: Study Objective: To compare phenytoin pharmacokinetics following administration of an oral suspension and a rectal suppository formulated with a polyethylene glycol base.
Design: Unblinded, single-dose, randomized, crossover trial.
Setting: University-affiliated pharmacokinetics and biopharmaceutics laboratory.
Subjects: Six healthy subjects.
Intervention: Subjects were given a single 200-mg dose of phenytoin as an oral suspension and a rectal suppository separated by a 1-week washout.
Measurements and Main Results: Blood for plasma phenytoin concentrations was obtained at baseline and 0.5, 1, 2, 4, 6, 8, 10, 12, and 24 hours after administration. Plasma was analyzed by high-performance liquid chromatography (coefficient of variation < 6%) for total phenytoin concentration. Phenytoin maximum concentration (Cmax), time to Cmax (Tmax), time to first measurable concentration (Tlag), and area under the curve from time zero to time of last measurable concentration (AUClast) were estimated for oral and rectal administration by WinNonlin (v 1.1) and compared using Wilcoxon's signed rank test (p<0.05 for statistical significance). Two subjects did not have detectable plasma phenytoin concentrations after rectal administration. For the other four subjects, median rectal Cmax was significantly lower than oral Cmax (0.4 vs 1.9 microg/ml, p=0.028), median rectal Tmax did not differ from oral Tmax (11.9 vs 8.0 hrs, p=0.465), and median rectal AUClast, although highly variable, was significantly lower than oral AUClast (5.4 vs 36.2 microg x hr/ml, p=0.046). No Tlag was seen after oral administration, but with rectal administration the median Tlag was 2 hours. The estimated relative bioavailability of rectal phenytoin suppositories based on AUC0-24 was 4.7%, with individual values ranging from 0-58.3%.
Conclusion: It appears that absorption of phenytoin from polyethylene glycol rectal suppositories in healthy subjects is highly variable and unpredictable. Thus this formulation is not recommended.
Databáze: MEDLINE
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