Inhibitory effect of propylthiouracil-induced hypothyroidism in rat on oxidative drug metabolism.
The effect of propylthiouracil (PTU) pretreatment on in vivo and in vitro oxidative drug metabolism was determined in the rat. Whereas pentobarbital sleeping time (PBST) and zoxazolamine paralysis time (ZZPT) were used as indices of in vivo drug metabolizing activity, biotransformation of aminopyrine and aniline by hepatic microsomal preparations were used as indices of in vitro drug metabolizing enzymes activities. PTU pretreatment significantly prolonged both PBST and ZZPT. Whereas PTU did not affect microsomal protein concentration or cytochrome P-450 content, it significantly decreased microsomal cytochrome c reductase and aniline hydroxylase activities. These changes in enzymatic activities were observed in microsomal preparations from either non-fasted or 24-hr fasted rats. Our results suggest that PTU-induced hypothyroidism modifies the metabolism and effectiveness or toxicity of concomitantly administered drugs.
Raheja
K L
KL
Linscheer
W G
WG
Chijiiwa
K
K
Iba
M
M
D000632:Aminopyrine / Q000378:metabolism; D000814:Aniline Compounds / Q000378:metabolism; D000818:Animals; D001711:Biotransformation / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D007037:Hypothyroidism / Q000378:metabolism*; D008099:Liver / Q000378:metabolism*; D008297:Male; D010424:Pentobarbital / Q000378:metabolism; D011441:Propylthiouracil / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D015049:Zoxazolamine / Q000378:metabolism
D000814:Aniline Compounds; D000632:Aminopyrine; D011441:Propylthiouracil; D003577:Cytochrome P-450 Enzyme System; D015049:Zoxazolamine; D010424:Pentobarbital; C023650:aniline