PMID- 10328562
OWN - NLM
STAT- MEDLINE
DCOM- 19990629
LR  - 20190719
IS  - 0918-6158 (Print)
IS  - 0918-6158 (Linking)
VI  - 22
IP  - 4
DP  - 1999 Apr
TI  - Effects of fatty acid glycerol esters on intestinal absorptive and secretory 
      transport of ceftibuten.
PG  - 402-6
AB  - The effects of fatty acid glycerol esters and Tweens on the intestinal transport 
      of ceftibuten were studied using a diffusion chamber system. The apparent 
      permeation coefficient (P(app)) was used as an index of the mucosal permeability 
      to ceftibuten. The P(app) markedly increased by the addition of hexaglycerol 
      monostearate (HGMS) or hexaglycerol sesquistearate (HGSS) under an H+-gradient 
      condition, while hexaglycerol tristearate (HGTS) and Tweens showed no effect on 
      the absorptive ceftibuten permeability. These results are in agreement with those 
      obtained in the previous study in the brush-border membrane vesicles. On the 
      other hand, in the absence of an H+-gradient, the S-to-M transport of ceftibuten 
      was proven to be significantly higher than the M-to-S one. In addition, either 
      ATP-depletion of the mucosa or the addition of probenecid proved to enhance 
      significantly the permeability of ceftibuten. These findings suggest the 
      existence of an active secretory transport system for ceftibuten in the jejunal 
      mucosa. To estimate potential effects of glycerol esters on efflux pumps as well 
      as peptide transporters, the mucosal-to-serosal (M-to-S) and serosal-to-mucosal 
      (S-to-M) permeability in the presence of the esters was further examined. HGMS, 
      HGSS and HGTS markedly enhanced the M-to-S but not the S-to-M transport in the 
      ATP-depleted jejunum without an H+-gradient, in which conditions contributions of 
      both peptide transporter and efflux pump should be substantially small. HGMS and 
      HGSS significantly enhanced the M-to-S ceftibuten transport in the ATP-depleted 
      jejunum with an H+-gradient (p<0.01 vs. M-to-S transport without surfactant under 
      the same conditions). Whereas, these glycerol esters were found hardly to affect 
      the P(app) of the S-to-M transport. These results indicate that the enhanced 
      intestinal transport of ceftibuten due to the glycerol esters may be based on 
      their effects on peptide transporters but neither on efflux pumps nor on the 
      passive permeation routes.
FAU - Koga, K
AU  - Koga K
AD  - Division of Pharmaceutical Information, Faculty of Pharmaceutical Sciences, 
      Hokuriku University, Kanazawa, Japan.
FAU - Murakami, M
AU  - Murakami M
FAU - Kawashima, S
AU  - Kawashima S
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - Japan
TA  - Biol Pharm Bull
JT  - Biological & pharmaceutical bulletin
JID - 9311984
RN  - 0 (Cephalosporins)
RN  - 0 (Esters)
RN  - 0 (Fatty Acids)
RN  - 0 (Surface-Active Agents)
RN  - 8L70Q75FXE (Adenosine Triphosphate)
RN  - IW71N46B4Y (Ceftibuten)
RN  - PDC6A3C0OX (Glycerol)
SB  - IM
MH  - Adenosine Triphosphate/metabolism
MH  - Animals
MH  - Biological Transport
MH  - Ceftibuten
MH  - Cephalosporins/*pharmacokinetics
MH  - Esters
MH  - Fatty Acids/chemistry/*pharmacology
MH  - Glycerol/*chemistry
MH  - Intestinal Absorption/*drug effects
MH  - Male
MH  - Rats
MH  - Rats, Wistar
MH  - Surface-Active Agents
EDAT- 1999/05/18 00:00
MHDA- 1999/05/18 00:01
CRDT- 1999/05/18 00:00
PHST- 1999/05/18 00:00 [pubmed]
PHST- 1999/05/18 00:01 [medline]
PHST- 1999/05/18 00:00 [entrez]
AID - 10.1248/bpb.22.402 [doi]
PST - ppublish
SO  - Biol Pharm Bull. 1999 Apr;22(4):402-6. doi: 10.1248/bpb.22.402.