PMID- 8456076
OWN - NLM
STAT- MEDLINE
DCOM- 19930422
LR  - 20190818
IS  - 0724-8741 (Print)
IS  - 0724-8741 (Linking)
VI  - 10
IP  - 2
DP  - 1993 Feb
TI  - Mass balance approaches for estimating the intestinal absorption and metabolism 
      of peptides and analogues: theoretical development and applications.
PG  - 271-5
AB  - A theoretical analysis for estimating the extent of intestinal peptide and 
      peptide analogue absorption was developed on the basis of a mass balance approach 
      that incorporates convection, permeability, and reaction. The macroscopic mass 
      balance analysis (MMBA) was extended to include chemical and enzymatic 
      degradation. A microscopic mass balance analysis, a numerical approach, was also 
      developed and the results compared to the MMBA. The mass balance equations for 
      the fraction of a drug absorbed and reacted in the tube were derived from the 
      general steady state mass balance in a tube: [formula: see text] where M is mass, 
      z is the length of the tube, R is the tube radius, Pw is the intestinal wall 
      permeability, kr is the reaction rate constant, C is the concentration of drug in 
      the volume element over which the mass balance is taken, VL is the volume of the 
      tube, and vz is the axial velocity of drug. The theory was first applied to the 
      oral absorption of two tripeptide analogues, cefaclor (CCL) and cefatrizine 
      (CZN), which degrade and dimerize in the intestine. Simulations using the mass 
      balance equations, the experimental absorption parameters, and the literature 
      stability rate constants yielded a mean estimated extent of CCL (250-mg dose) and 
      CZN (1000-mg dose) absorption of 89 and 51%, respectively, which was similar to 
      the mean extent of absorption reported in humans (90 and 50%). It was proposed 
      previously that 15% of the CCL dose spontaneously degraded systematically; 
      however, our simulations suggest that significant CCL degradation occurs (8 to 
      17%) presystemically in the intestinal lumen.(ABSTRACT TRUNCATED AT 250 WORDS)
FAU - Sinko, P J
AU  - Sinko PJ
AD  - College of Pharmacy, Rutgers University, Piscataway, New Jersey 08855-0789.
FAU - Leesman, G D
AU  - Leesman GD
FAU - Amidon, G L
AU  - Amidon GL
LA  - eng
GR  - BRSG 4-23444/RS/DRS NIH HHS/United States
GR  - GM37188/GM/NIGMS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Pharm Res
JT  - Pharmaceutical research
JID - 8406521
RN  - 0 (Insulin)
RN  - 0 (Peptides)
RN  - 69K7K19H4L (Cefaclor)
RN  - 8P4W949T8K (Cefatrizine)
SB  - IM
MH  - Cefaclor/pharmacokinetics
MH  - Cefatrizine/pharmacokinetics
MH  - Humans
MH  - Insulin/pharmacokinetics
MH  - *Intestinal Absorption
MH  - Models, Biological
MH  - Peptides/chemistry/*pharmacokinetics
MH  - Permeability
OTO - NASA
OT  - NASA Discipline Number 18-10
OT  - NASA Discipline Regulatory Physiology
OT  - NASA Program Space Physiology and Countermeasures
OT  - Non-NASA Center
FIR - Amidon, G L
IR  - Amidon GL
IRAD- U Michigan, Ann Arbor, Coll Pharmacy
EDAT- 1993/02/01 00:00
MHDA- 1993/02/01 00:01
CRDT- 1993/02/01 00:00
PHST- 1993/02/01 00:00 [pubmed]
PHST- 1993/02/01 00:01 [medline]
PHST- 1993/02/01 00:00 [entrez]
AID - 10.1023/a:1018999130076 [doi]
PST - ppublish
SO  - Pharm Res. 1993 Feb;10(2):271-5. doi: 10.1023/a:1018999130076.