The use of a nonlinear absorption model in the study of ascorbic acid bioavailability in man.
A two-compartment disposition model of ascorbic acid (AA) pharmacokinetics with saturable and time-constrained intestinal absorption was developed. The model was fitted to pharmacokinetic data obtained after oral administration to nine healthy volunteers of two effervescent dosage forms differing in AA content: Celaskon 60 mg (CK60) and Celaskon 500 mg (CK500). It was demonstrated that in the case of CK500 less than 30% of the dose was absorbed as compared with CK60. Parameters of the AA nonlinear absorption kinetics were assessed by simultaneous fitting of mean concentration-time data for both doses and placebo. The relatively short duration of absorption found (3.2 h) can explain the failure of past attempts to increase the AA bioavailability using sustained-release dosage forms. Model simulation showed that the ingestion of 60 mg with 3-4 h intervals is optimal for maximal bioavailability of AA.
Piotrovskij
V K
VK
Institute of Preventive and Clinical Medicine, Bratislava, Czechoslovakia.
Kállay
Z
Z
Gajdos
M
M
Geryková
M
M
Trnovec
T
T
D000328:Adult; D001205:Ascorbic Acid / Q000097:blood / Q000493:pharmacokinetics*; D001682:Biological Availability; D005260:Female; D006801:Humans; D008297:Male; D008962:Models, Theoretical; D017711:Nonlinear Dynamics; D013607:Tablets
D013607:Tablets; D001205:Ascorbic Acid