TY - JOUR
T1 - Structure‐Related Inhibitory Effect of Quinolones on Alky1‐Xanthine Elimination in Rats
AU - Hasegawa, Takaaki
AU - Kuzuya, Takafumi
AU - Apichartpichean, Ruttikorn
AU - Nadai, Masayuki
AU - Nitta, Atsumi
AU - Takagi, Kenzo
AU - Nabeshima, Toshitaka
PY - 1991/7
Y1 - 1991/7
N2 - Abstract: To investigate the relationship between the chemical structures of quinolones, enoxacin (ENX) and its analogues, and their metabolic inhibitory effects on theophylline, a xanthine derivative closely related to theophylline, 1‐methyl‐3‐propylxanthine (MPX), was used as a model of theophylline in rats. The disappearance of MPX from plasma was significantly delayed by treatment with ENX and analogue A (derivatives without substituent group at both 3′‐ and 5′‐carbon atom in the piperazinyl ring): total body clearance of MPX was significantly decreased by approximately 50%. However, analogue A was converted into ENX in the rat body (about 14% of dose). Analogues B and C (derivatives with substituent group at 3′‐ or 5′‐carbon atom in the piperazinyl ring) had little or no effect on MPX disposition. No significant change in the volume of distribution of MPX was observed after coadministration with these quinolones. The results of this study indicate that the substitutions on 3′ and 5′‐carbon atoms of piperazinyl ring at 7‐position of the quinolone molecule may play important role in the inhibition of theophylline metabolism. 1991 Nordic Pharmacological Society
AB - Abstract: To investigate the relationship between the chemical structures of quinolones, enoxacin (ENX) and its analogues, and their metabolic inhibitory effects on theophylline, a xanthine derivative closely related to theophylline, 1‐methyl‐3‐propylxanthine (MPX), was used as a model of theophylline in rats. The disappearance of MPX from plasma was significantly delayed by treatment with ENX and analogue A (derivatives without substituent group at both 3′‐ and 5′‐carbon atom in the piperazinyl ring): total body clearance of MPX was significantly decreased by approximately 50%. However, analogue A was converted into ENX in the rat body (about 14% of dose). Analogues B and C (derivatives with substituent group at 3′‐ or 5′‐carbon atom in the piperazinyl ring) had little or no effect on MPX disposition. No significant change in the volume of distribution of MPX was observed after coadministration with these quinolones. The results of this study indicate that the substitutions on 3′ and 5′‐carbon atoms of piperazinyl ring at 7‐position of the quinolone molecule may play important role in the inhibition of theophylline metabolism. 1991 Nordic Pharmacological Society
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U2 - 10.1111/j.1600-0773.1991.tb00399.x
DO - 10.1111/j.1600-0773.1991.tb00399.x
M3 - Article
C2 - 1946192
AN - SCOPUS:0025877260
SN - 0901-9928
VL - 69
SP - 5
EP - 8
JO - Pharmacology & Toxicology
JF - Pharmacology & Toxicology
IS - 1
ER -