Effect of protein and calorie malnutrition on drug metabolism in rat - in vitro.
OBJECTIVE
To study the effect of protein and calorie malnutrition on in vitro drug metabolism of protein and calorie malnourished juvenile and adult rats.


METHODS
Microsomal incubation was used as a means of monitoring drug metabolism changes, HPLC was employed to quantify metabolites and enzyme immunoassay (EIA) was used for rat growth hormone (rGH) monitoring.


RESULTS
Protein and calorie malnutrition significantly decreased levels of microsomal protein and total P450. Microsome of protein and calorie malnourished rats showed impaired testosterone 16alpha- and 2alpha- hydroxylation (CYP2C11), testosterone 6beta-hydroxylation (CYP3A), and testosterone 7alpha-hydroxylation (CYP2A1). Testosterone 16beta-hydroxylation (CYP2B1) did not show any significant change, neither in capacity nor affinity. The quantity and the secretion pattern of rGH were not altered in protein and calorie malnourished rats compared to those in healthy animals.


CONCLUSIONS
Serum albumin is not a good indicator of malnutrition. The capacity and affinity of CYP2C11, CYP3A and CYP2A1 were compromised by protein and calorie malnutrition. The impairment of drug metabolism in protein and calorie malnourished rats was not caused by the alteration of rGH.
Mao
Z L
ZL
Astellas Pharma US, 3 Parkway North, Deerfield, Illinois 60015, USA. lily.mao@us.astellas.com
Tam
Y K
YK
Coutts
R T
RT
D000818:Animals; D003577:Cytochrome P-450 Enzyme System; D008297:Male; D008862:Microsomes, Liver / Q000201:enzymology / Q000378:metabolism*; D004364:Pharmaceutical Preparations / Q000378:metabolism*; D011502:Protein-Energy Malnutrition / Q000201:enzymology / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley
D004364:Pharmaceutical Preparations; D003577:Cytochrome P-450 Enzyme System