[Relative bioavailability of paracetamol in suppositories preparations in comparison to tablets].
Relative Bioavailability of Paracetamol as Suppositories Compared to Tablets. The relative bioavailability of paracetamol (CAS 103-90-2) in ben-u-ron 500 mg and ben-u-ron 1000 mg suppositories (test formulations) was compared with that of Benuron tablets 500 mg (reference product) in an open, intraindividual, 3-period-changeover-study in 18 healthy subjects. Plasma concentrations of paracetamol were determined using a specific and sensitive HPLC method with UV detection. For the assessment of bioavailability AUC, Cmax, tmax and HVD were used as pharmacokinetic characteristics. Bioequivalence of the rectal formulations was tested by calculating 90% confidence intervals using the Two-one-sided-t-tests-procedure and log-transformed data of AUC and Cmax. For AUC the confidence intervals were required to be in the 80 and 125% range, for Cmax between 70 and 143% (inclusion rule). Data from 17 subjects could be evaluated. Bioavailability of paracetamol was 89 and 90% for the 500 and 1000 mg suppositories, respectively compared with that of the 500 mg reference tablets. Mean maximum paracetamol plasma concentrations (Cmax) were 3.55 and 6.02 or 7.16 mg/l after administration of the 500 and 1000 mg suppositories or the 500 mg tablets, respectively. These maximum concentrations were achieved 2.0, 2.7 and 0.6 h (tmax) after administration of the respective preparations. The corresponding HVD values were 4.3, 5.2 and 2.0 h, respectively. After dose adjustment of the results for the 1000 mg suppositories relative bioavailabilities of paracetamol from both rectal formulations exceeded 80% of that from the tablets.(ABSTRACT TRUNCATED AT 250 WORDS)
Zentrallaboratorium Deutsher Apotheker, Eschborn.
H
H
Blume
S L
SL
Ali
M
M
Elze
J
J
Krämer
G
G
Wendt
M E
ME
Scholz
D000082:Acetaminophen / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D000328:Adult; D001682:Biological Availability; D002851:Chromatography, High Pressure Liquid; D005260:Female; D006801:Humans; D008297:Male; D013056:Spectrophotometry, Ultraviolet; D013488:Suppositories; D013607:Tablets; D013810:Therapeutic Equivalency
D013488:Suppositories; D013607:Tablets; D000082:Acetaminophen
Relative Bioverfügbarkeit von Paracetamol in Suppositorien-Zubereitungen im Vergleich zu Tabletten.