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Absorption of Phenytoin from Rectal Suppositories Formulated with a Polyethylene Glycol Base
Author(s) -
Burstein Aaron H.,
Fisher Karen M.,
McPherson M. Lynn,
Roby Carol A.
Publication year - 2000
Publication title -
pharmacotherapy: the journal of human pharmacology and drug therapy
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.227
H-Index - 109
eISSN - 1875-9114
pISSN - 0277-0008
DOI - 10.1592/phco.20.6.562.35157
Subject(s) - medicine , suppository , cmax , pharmacokinetics , phenytoin , crossover study , rectal administration , oral administration , bioavailability , anesthesia , gastroenterology , pharmacology , placebo , epilepsy , alternative medicine , pathology , psychiatry
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 (C max ), time to C max (T max ), time to first measurable concentration (T lag ), and area under the curve from time zero to time of last measurable concentration (AUC last ) were estimated for oral and rectal administration by WinNonlin (v 1.1) and compared using Wilcoxons 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 C max was significantly lower than oral C max (0.4 vs 1.9 μg/ml, p=0.028), median rectal T max did not differ from oral T max (11.9 vs 8.0 hrs, p=0.465), and median rectal AUC last , although highly variable, was significantly lower than oral AUC last (5.4 vs 36.2 μg•hr/ml, p=0.046). No T lag was seen after oral administration, but with rectal administration the median T lag was 2 hours. The estimated relative bioavailability of rectal phenytoin suppositories based on AUC 0–24 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.