Bioavailability of racemic ibuprofen and its lysinate from suppositories in rabbits.
Plasma concentration (C)-time (t) plots of ibuprofen from suppositories in rabbits are characterized by the sum of two exponentials, C = Be-lambda 2t-Ae-lambda 1t. When A exceeds B, there is a lag time (tlag = tc = 0) before the start of absorption. Evidence for dose-dependent area under the curve (AUC) of C versus t values is presented with the implication that elimination rate constants (ke) decrease and the AUC/dose ratio increase with dose. The lack of significant differences between the AUC values from suppository and the intravenous studies with similar doses implies complete absorption of ibuprofen from all the suppositories studied. The absorption rate constants (ka) were estimated on the presumption of complete absorption and dose-dependent elimination. Ibuprofen lysinate was absorbed significantly more readily than the free acid from suppositories. The lysinate suppository with a lipophilic surfactant had a higher absorption rate constant than that with a hydrophilic surfactant. The ka values did not significantly differ for a twofold difference in dose. Equations were developed to calculate true AUC and area under the moment curve (AUMC) values when A exceeds B, and to transform C versus t plots to the origin with A' = A = B. Times of maximum peak heights, mean residence (MRT), and mean absorption times (MAT = 1/ka) of suppositories when A > B are shown to differ by the lag time (tc = 0) from the plots of C versus t transposed to the origin. Although corrected AUC values when A > B are equal to the AUC values of C versus t plots transposed to the origin (A' = A = B), the corrected AUMC values when A > B significantly differ from the AUMC values for the C versus t plots transposed to the origin.
Hermann
T W
TW
Department of Physical Chemistry, College of Pharmacy, K. Marcinkowski University School of Medical Sciences, Poznań, Poland.
Gtówka
F K
FK
Garrett
E R
ER
D000818:Animals; D001682:Biological Availability; D004305:Dose-Response Relationship, Drug; D005260:Female; D007052:Ibuprofen / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics*; D008239:Lysine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D008297:Male; D011817:Rabbits; D013237:Stereoisomerism; D013488:Suppositories; D013501:Surface-Active Agents / Q000494:pharmacology
D013488:Suppositories; D013501:Surface-Active Agents; D008239:Lysine; C016106:solufenum; D007052:Ibuprofen